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D.B.  Weldon  Library 
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empreinte. 

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symbols  V  signifie  "FIN  ". 

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film*s  *  des  taux  de  reduction  diffirents. 
Lorsque  le  document  est  trop  grand  pour  *tre 
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de  Tangle  sup*rieur  gauche,  de  gauche  *  droite. 
at  de  haut  an  bas.  an  pranant  le  nombre 
d'images  n*cessaire.  Les  diagrammes  suivants 
illustrent  la  m*thode. 


1 

2 

3 

4 

5 

6 

MICROCOPY    RESOLUTION    TEST   CHART 

ANSI  (H.fl   ISO   IE  SI   CHART   Nr     ? 


1.0 


I.I 


1.25 


1.4 


m 

2.2 
ZO 

1.8 


^     APPLIED  IIVMGE 


PHYSIOLOGY  AND  PATHOLOGY 

OF  THE 

CEREBROSPINAL  FLUID 


V)<^^ 


THE  MACMILI.AN  COMPANY 

NEW  YORK         rnsTON   -    CIMCAt.O   •    HALLAS 
ATI-ANTA    •    SAN    FKASCISCO 

MACMILI.AN  &   CO  ,  riM:Tri> 

LONDON   •    POMHAV   •    CALCITIA 
HKLhOIRNK 

THE  MACMILLAN  CO    OF  CANADA.  Lto. 

TORONTO 


Choroid  Plexus. 


Physiology  and  Pathology 

of  the 

Cerebrospinal  Fluid 


BY 


WILLIAM  BOYD 

Profeuor  ot  Pathology,  Univenity  of  Manitoba 
Pathologist,  Winnipeg  General  Hoipiul 


THE  MACMILLAN  COMPANY 

1920 

All  righta  reserved 


6195 

liv  Tin;    MAtMlI.I.AN   fKMl'ANY 


Si't  up  uiiil  >'Urirnt.\i.,(l,      I'liliU-lii'il.  .hull',  r.t-0 


TO 

MV  TEAChE  I  AND 
CHIEF 

UYROM   BRAMWELL 


Cet  enfant  a  de  I'eau  dans  le  tcte,  dit  le  vulgaire:  cet  enfant 

est  hydrocephale,  dit  gravement  le  medecin,  rcpetant  litteralc- 

ment  par  un  mot  grec  ce  que  dit  I'ignorant  dans  sa  propre 

langue.     Mais  quelle  est  cette  eau?     d'oii  vient-elle?     Voila 

ce  dont  les  medecins  auraient  du  s'occuper. 

Magendie. 


(    ' 


PREFACE 

The  object  of  this  book  is  to  present  some  of  the  fascinating 
physiological  problems  connected  with  the  cerebrospinal  fluid, 
and  to  show  how  they  are  related  to  the  pathological  problems 
whidi  more  directly  concern  the  clinician.  Not  until  the 
method  of  production  and  absorption  of  the  fluid  is  completely 
understood  can  there  be  any  hope  of  solving  the  age-long  prob- 
lem of  the  treatment  of  hydrocephalus;  not  until  the  details 
of  the  circulation  of  the  fluid  have  been  mastered,  can  intra- 
spinal injections  of  drugs  and  sera  be  expected  to  fulfill  the 
hopes  of  the  thprapeutist. 

Any  means  which  will  facilitate  the  difficult  diagnosis  of  dis- 
eases of  the  central  nervous  system  is  of  value,  and  the 
cerebrospinal  fluid,  which  bathes  its  deepest  recesses  and  washes 
the  very  nerve  cells  and  filers  themselves,  is  in  truth  a  mirror 
which  reflects  every  change  taking  place  in  that  system. 


IX 


CONTENTS 


CHAPTER 

I 

II 

III 

IV 

V 

VI 

VII 

VIII 

IX 

X 

XI 

XII 

XIII 


XIV 


XV 


PART  I 
GENERAL  page 

Introductory          3 

Anatomical  Considerations 6 

Origin  and  Destination  of  the  Fluid      ...  14 

The  Circulation  of  the  Fluid 23 

Functions  of  the  Cerebrospinal  Fluid    ...  29 

Pressure  of  the  Cerebrospinal  Fluid      .     •     •  33 

Lumbar  Puncture 2P 

Physical  Properties 4^ 

Chemical  Composition 49 

fin 
Cytology "" 

Wassermann  Reaction 73 

Colloidal  Gold  Reaction  of  Lange     .     .     ■     ■     79 

Bacteriological  Methods ^ 

PART  II 

SPECIAL 

Meningitis        9^ 

Meningococcal  meningitis 9^ 

Pneumococcal  meningitis 97 

Streptococcal  meningitis 99 

Tuberculous  meningitis '°° 

Meningitis  due  to  other  organisms i'^4 

Serous  meningitis '°5 

Syphilis  OF  the  Central  Nervous  System     .     .no 

Early  syphilis  . \\\ 

Cerebrospinal  syphilis "J 

Tabes  dorsahs ^^5 

General  paresis "7 

Juvenile  general  paresis i^o 

xl 


XII 

CHAFTEIl 
XVI 


XVII 


XVIII 


XiX 


XX 


CONTENTS 

PAGE 

Organic  Disease  of  the  Brain ^^i 

Cerebral  tumor '■^3 

Cerebral  abscess *-4 

Cerebral  haemorrhage ^^° 

Cerebral  thrombosis '^7 

Encephalitis '^7 

Hydrocephalus  .         '-° 

Concussion;  shell  shock '3' 

Oedema  of  the  brain '3' 

Organic  Disease  of  the  Spinal  Cord  .     .     .     •  i33 

Tumor  of  the  spinal  cord *33 

Syringomyelia '33 

Acute  myelitis       .      . '35 

Acute  anterior  poliomyelitis '35 

Subacute  combined  degeneration 14° 

Multiple  sclerosis '4' 

Herpes  zoster '•+' 

Mental  Diseases '43 

Manic-depressive  insanity '43 

Epilepsy '44 

Dementia  praecox '44 

Alcoholism       . '45 

Idiocy  and  imbecility '45 

General  Diseases '4^ 

Diabetes '46 

Uraemia '4o 

Chorea        '4» 

Mumps '49 

Pneumonia '5' 

Sleeping  sickness '5' 

Trichinosis '5^ 

Therapeutics ^55 

Lumbar  punctnre ;    .•.    "     "   ^^| 

Serum  trtitn^ent  of  cerebrospinal  meningitis  .      .158 

Tuberculous  meningitis '62 

Poliomyelitis .."■*■    '9*^ 

Intraspinal  treatment  of  neuro-syphilis       .      .      .    163 
Tetanus '7° 


LIST  OF  ILLUSTRATIONS 

IN  BLACK  AND  WHITE 

PACE 

Diagrammatic  representation  of  distribution  of  the  cerebro- 
spinal fluid 

Lumbar  puncture  needle  in  arachnoid  sac '2 

Cassidy  and  Page's  Spinal  Pressure  Set 34 

The  bony  landmarks  for  lumbar  puncture 3^ 

Mastic  test  in  General  Paresis 85 

COLORED  PLATES 

Choroid  Plexus Frontispiece 

Normal  cell  count °3 

Meningococcal  Meningitis 93 

Pneumococcal  Meningitis 97 

Streptococcal  Meningitis 99 

Lymphocytosis  in  General  Paresis ^^5 


'■i 


PART  I 
GEXERAL 


PHYSIOLOGY  AND  PATHOLOGY  OF 
THH  CEREBROSPINAL  FLUID 


(  IIAI'IKR  F 
IXTRODrCTORV 

The  fluids  of  the  IkkIv  have  aroused  interest  and  specula- 
tion from  times  immemorial.  Oi)^ervations  on  the  blood  and 
the  urine  are  to  l)e  found  in  the  earliest  medical  works,  and 
the  speculations  as  to  their  function  and  composition  would 
fill  a  lil)rary  of  volumes.  Although  it  was  hardl)  to  be  ex- 
pected that  the  same  amount  of  interest  should  have  been 
aroused  bv  the  cerebrospinal  fluid,  yet  reference  to  the  con- 
tents of  the  cerebral  ventricles  is  made  by  many  of  the  earliest 
writers.  Galen,  Vesalius,  and  Valsalva  all  note  its  preseno 
and  it  would  have  been  remarkable  if  the  existence  of  a 
watery  fluid  in  the  interior  of  the  skull  should  have  escaped 
such  an  accomplished  observer  as  Aristotle.  Cotugno  in 
}jCt2  and  Ilaller  in  1766  both  described  the  existence  of  a  clear 
limpid  fluid  not  only  in  the  ventricles  of  the  brain,  but  al.so 
in  the  sjiace  between  the  membranes  and  the  convolutions. 

Our  modern  interest  in  the  fluid  dates  from  the  masterly 
ob.servations  and  equally  masterly  description  of  I\raj]rendie  in 
iSr5.  It  was  he  who  first  realized  the  intimate  connection 
between  the  fluid  in  the  ventricles  and  that  in  the  subarchnoid 
space,  and  also  the  physiological  possibilities  of  a  fluid  which 
comes  into  such  close  relation  with  the  central  nervous  system. 
His  description  of  the  distribution  of  the  fluid,  and  of  the  ef- 
fects of  varying  intracranial  pressure  is  of  sufTicient  interest 
to  bear  quotation : 

Entre  la  pie-mere  et  I'arachnoide  se  touve  un  liquide  que 
je  propose  d'appeler  cerebro-spinale ;  il  existe  chez  rhomme  et 

3 


ril^SroUHV   AND   I'ATIIOUKJY   OF  TIIU  CEREBROSPINAL   FLUID 


chcz  ti)us  tnaintiiifCTcs.  II  scrt  a  cuiiililcr  le  vide  (lui  cxistcrait 
cntrc  Ic  ctT\  tan  ct  Ic  cniiie  osscu:; ;  il  >c  rcj;ciKTc  avcc  rapiditc, 
pent  circulcr  a  travcrs  Ics  vcutriculcs  ccr'-'traux  ct  Ics  cspaces 
suus-uraclinoidiciis  dit  cirvcaii  ct  dc  la  iiiocllc.  An  niunient 
dc  I'cxpiratioii  Ic  ccrvcau  sc  gmillc;  le  liipiidc  ccrcl>r()-spiiialc 
passc  du  cniiic  <laiis  Ic  canal  vcrtcliral.  (Jnand  on  augnincute 
la  prcssiun  tin  li(inidc,  tm  prodnit  dcs  plicnoinciics  dc  paralysie 
ct,  d'antrc  part,  ijnantl  pir  nnc  unvcrlnrc  on  provoque  Tissu 
dc  cc  li(inidc.  Ic  ctrvcan  ct  la  niocllc  n'clant  proteges,  il  snrvicnt 
nnc  dcliilitc  ct  nnc  faililcssc  gcncralc  dc  I'aninial. 

In  iS(>i  <Jninckc  introdnccd  the  operation  of  lumbar  pnnc- 
turc  in  the  living  >ul)jcct,  and  an  enormous  impetus  was  at 
once  given  to  the  >tudy  of  the  llnid  in  various  patlujlogical 
Conditions.  I.uinliar  puncture  was  originally  introduced  for 
therapeniic  i)urpu>es,  :■-  a  lU'-ans  of  lowering  an  ,i  niormally 
higli  introcranial  pressure.  Soon,  however,  the  diagnostic 
p()>>iI)ililiL'>  came  to  ovcr>ha(low  those  oi  therapeutics,  and  the 
I'Vcnch  school,  led  hy  \\  idal.  Sicard,  and  Ravaut,  showed  in 
i<;"i  tliat  \cry  important  and  characteristic  changes  occurred 
in  the  e\titlii!.;y  ni  the  ihiid  in  certain  nervous  diseases,  notahly 
tiio.^c  as>oci;itc<l  uitli  .-yphilis.  Constant  changes  in  the  tUiid 
were  al>o  found  in  conditions  of  acute  meningitis. 

It  was  soi.n  realized  that  just  as  an  examination  of  the 
lilood  can  aiTord  valual)lc  information  regarding  pathologicd 
changes  in  the  tissues  through  which  it  circulates,  so  the  mor- 
hid  Conditions  atTccting  the  central  nervous  system  are  in 
ni:in\  c;i>c^  rcilcctcd  uitii  a  rcmarkahle  degree  of  accuracy  hy 
tlie  amhient  tluid  which  bathes  its  remotest  recesses  and  re- 
ceives the  pniducts  of  its  metabolism.  As  the  original  some- 
what coarse  tcchniciuc  becnines  more  and  more  retineil  the 
diagnostic  pns-ibiliiies  of  spinal  tluid  examination  become  ever 
greater,  and  if  such  tests  as  the  Wassermann  and  the  colloidal 
gold  are  only  the  forerunners  of  a  host  of  others,  there  is 
reason  to  hope  that  characteristic  changes  will  ultimately  \x 
found  in  the  great  majority  of  ticrvons  and  mental  diseases. 

Alreadv  it  ha-  '-een  established  that  indications  of  diag- 
nostic importance  in.ay  be  afforded  by  the  spinal  fluid  in  other 


INTROOUCTORV  5 

conditions  than  nervous  afTcctions.  It  will  h:  seen  later  tliat 
in  Mich  j^'oneral  diseases  as  diaU-tes  and  ur:e»'iia  there  are 
important  chaiifjes  in  the  lluid.  I'"ven  in  the  very  early  sta^jes 
of  syphilis  heforc  there  are  atiy  clinical  indications  of  involve- 
ment of  the  nervous  system  the  spinal  nui<i  may  present  a 
characteristic  picture.  In  trichiniasis  it  is  often  invaded  hy 
the  trichina  spiralis  l)ef()re  any  somatic  symptoms  of  the  dis- 
ease have  made  their  appearance.  Slecpinjj  sickness  is  an 
example  of  a  disease  in  which  the  final  diajjnosis  depends  on 
the  demonstration  of  the  parasite  in  the  cerebrospinal  fluid. 

Cireat  as  have  l)een  the  diagnostic  advances  in  this  sphere, 
the  therapeutic  possibilities  are  now  heginninp  to  attract  even 
greater  attention.  The  simple  drainage  of  the  suI)arachnoid 
space  and  the  ventricles  l>y  himltar  puncture  has  provc<l  of 
great  value  in  a  multitude  of  conditions,  and  the  possibilities 
of  the  intradural  injection  of  sera  and  drugs  by  the  spinal 
and  cerebral  routes  arc  iu     l^ginning  to  Ix*  realized. 


RE. ERENCES 

TIallcr:     Pliysinloiric  in  <!cs  Mcnschcs.     1766. 

M.iRcndic:  ^fcnioirc  sur  tin  liqiiidc  qui  sc  troiivc  dans  le  crane  ct 
la  colnnne  vcrtehrale  do  I'liommc  ct  dcs  aiiimaux  niammi feres.  C. 
R.  .Acad,  dcs  .'Sciences.  10  Jan..  1SJ5. 

Quincke:  Die  T.umbalpunktion  des  Hydroccfalus.  Berl.  klin. 
Wchnschr..  17  Sept..  1891. 

Widal,  Sicard  ct  Ravaut:  Cytolopie  du  liquide  ccphalo-rachidien. 
Bull,  ct  incm.  Soc.  nicd.  d.  hop.  dc  Pari-;,  1901. 


Cll.M'TI'.R  II 

ANATOMIC. \l.  C()^■Sll)'•:l^\Tl(jXS 

The  ccrehnispiiial  lluid  iiccupic-;  tin.'  ventricle^  of  tlie  hrain, 
tlic  sukiracliiitml  >i)acc.  and  the  ccmral  canal  of  tlie  C(ird. 
Is  the  tluid  in  tlicse  three  res^ion^  ctnuinumis?  Is  it  affected 
in  cotiipiisitiini  hv  the  dit'fei-ent  tis-ues  with  whicii  it  finds  itself 
in  contact?  How  does  it  ('riL;inate,  and  what  is  it>  destina- 
tion? 'i'hesc  question^  cannot  he  an>\vere(l  without  a  consid- 
eration of  the  anatomical  relationsliiiis  i^i  the  cavities  which 
contain  the  lUiid,  and  of  the  histolot;ical  constitution  of  the 
structures  with  which  these  cavities  are  lined,  an<l  over  which 
the  Huid  has  to  jia.-s. 

THE  SUBARACHNOID  SPACE 

The  lirain  is  covered  hv  thn^e  metnhranes,  the  dura  mater, 
the  arachnoid  m.ati'r.  and  the  pia  mater,  aucl  between  these 
three  inemhranes  there  are  two  cavities,  the  subdural  cavity 
l)etween  the  dura  .and  arachnoid,  the  .-uliarachnoid  between 
the  arachnoid  and  pia.  The  dm-a  m;iter  is  a  thick,  ton.'^h, 
dense  membrane  of  iibrous  tissue  con>i'-tin,;,'  of  two  layers; 
an  outer  .adherent  to  the  w.ill  of  the  cr.'uiial  cavity  and  actin;.'^ 
as  a  periostetiin  for  th.at  w.ill,  and  rm  inner  covered  b\'  a 
sheet  of  endothelium.  The  two  layers  separate  in  places  to 
enclose  the  venou>  sinu-es  of  the  skull. 

The  sulidur.il  -j)ace  is  liounded  externally  by  the  inner  layer 

of  dur.'!  mater,  internallv  by  the  .arachnoid,  and  both  w.alls  are 

covered  bv  endothelium.     The  e.avity  is  more  jiotential  than 

real,    .and    contains   a    minute   quantitv   of   .a    Ivmph-lil-.e    Ihiid. 

There  is  no  cirnununicatiou  of  ;in\'  kind  between  the  subdural 

and    the    subar.aclHK  lid    -pace,      ('.ilnri'd    H'lids    injected    into 

th.e    su.!)'lu.r.:i!    -icicc  Jn   not    .'uinc.'ir   in   the    snbarnchnoid   sn.-ice. 

and   in  ha'morrh.aue   into  the   s!il)dural   ~pace  the  blnod   does 

6 


*<t 


5Ks?!^r^!5WHBr-T^^*a»s«'  's:-4fm-m£wsim^ 


ANATOMICAL    CONSIDnRATIOXS 


not  make  its  way  into  tlie  sul)araclin()iil  space.  The  I)arricr 
a|)|)ears  to  l)e  coiiii)lete  and  inipenelralile. 

W'lien  tlie  skull  caj)  is  renKAcd  a  nunilier  of  small,  roujjh, 
tuft-like  liodies  will  he  ohserved  j;alhcred  in  clusters  along  the 
line  of  the  superior  longitudinal  sinus.  These  are  the  Pacchi- 
onian hodi'-'s.  Thev  consist  of  invaginations  of  the  arachnoid 
carrving  the  dura  in  front  i>f  them,  and  arc  com])oscd  of 
spongy  tissue  continuous  with  the  spongy  areolar  tissue  which 
occupies  the  suharachnoid  si)ace.  They  are  thus  really  ex- 
tensions of  the  suharachnoid  sjjace.  They  project  for  the 
ino>t  part  into  the  superior  longitudinal  sinus.  \'arious  func- 
tions ha\e  heen  altrihuted  to  the  I'acchionian  hodies.  It  has 
often  heen  suggested  that  they  repre-ent  the  portal  through 
which  the  CLTcliros|iiual  tluid  ])asves  from  the  suharachnoid 
space  into  the  hloixl.  It  is  certain,  however,  that  any  function 
(  f  this  nature  which  they  may  possess  is  shared  by  other 
structures,  for  thcv  do  not  make  their  ai)iK'arance  till  the 
third  year,  and  are  not  present  in  any  numher  until  after 
the  age  of  ten.  Moreover  thev  arc  not  found  in  the  lower 
animals.     Thev  increase  considerahly  in  numher  in  old  age. 

The  arachnoid  mater  is  a  thin  non-vascular  niem!)rane, 
hoth  sides  of  which  are  covered  hy  a  layer  of  endothelium. 
It  forms  the  impcrmeahle  partition  between  the  subdural  and 
.subarachnoid  spaces.  It  clothes  the  brain  much  in  the  same 
wav  that  a  mantle  clothes  the  body,  that  is  to  say  it  does  not 
adapt  itself  closelv  to  the  folds  of  the  convolutions,  nor  docs 
it  dip  down  into  the  fissures. 

The  pia  mater  is  a  delicate,  higlily  vascular  membrane, 
which  is  traversed  bv  great  numbers  of  blood  vessels  on  their 
way  to  and  from  the  brain.  In  .spite  of  its  great  vascularity, 
however,  it  contains  no  capillaries,  and  in  consequence  it  takes 
no  part  in  the  absorption  of  the  fluid.  Its  relation  to  the 
brain  is  vcrv^  different  to  that  of  the  aracluioid  mater.  It  may 
l)e  compared  to  a  closelv  fitting  glove  which  adapts  itself  to 
every  fold  and  ussure  of  the  organ.  The  result  of  this  dif- 
ference in  the  two  membranes  is  that  the  space  which  inter- 
venes   between    them,    the    subarachnoid    space,    although    in 


8 


IMIVSIOI.OGY  AND   PATIIOI.OGV  OF  THE  CnREBROSPINAL  FLUID 


many  placos  very  narrow,  in  others  is  of  considerable  depth. 
'I  he  places  where  the  increase  in  depth  Ix'conies  marked  are 
named  cisterns,  ami  are  ihree  in  number.      ( l'"ii,^  I.) 

'Ilie  cisterna  magna  lie>  between  the  posterior  surface  of  the 
medulla  and  the  cerebellum,  and  is  formed  by  a  continuation 
upwards  of  the  posterior  part  of  the  sul_)arachnoid  space  of 
the  s])inal  canal.  It  communicates  directly  with  the  fourth 
ventricle,  for  into  it  open  the  various  foramina  situated  in 
the  membranous  roof  of  that  ventricle.  The  arachnoid,  in- 
steail  of  being  closely  retlected  over  the  surface  of  the  medulla 
and  cerebellum,  brids^o  across  the  interval  between  these  struc- 
tures, with  the  resuU  that  in  this  region  the  subarachnoid 
^pace  develops  into  a  veritable  ci>tern. 

The  cisterna  pontis,  a  prolongation  of  the  anterior  part  of 
tlie  spinal  ^-ubarachnoid  space,  nes  in  front  of  the  medulla, 
:ind  is  continuous  round  it  with  the  cisterna  m.agna.  Thus 
this  delicate  jiart  of  the  brain,  containing  as  it  does  so  many 
\ii.d  centers,  is  jirotected  in  a  most  efficient  manner  by  a 
regular  water  cushion. 

The  cisterna  basalis  is  formed  by  the  arachnoid  stretching 
across  between  the  two  temporal  poles,  is  of  large  size,  and 
comes  into  intimate  relationship  with  the  very  important  in- 
terpeduncular space,  where  many  of  the  inflanmiatory  condi- 
tions of  the  meninges  show  their  most  intense  manifestations. 

The  cerebrospinal  fluid  within  the  cranial  cavity  may  there- 
fore be  regarded  as  an  expan.se  of  water  with  rivers,  rivulets, 
and  a  few  deep  lakes.  This  analogy  must  not,  however,  give 
rise  to  the  conception  of  a  mass  of  fluid  in  a  motionless  and 
stagnant  .state.  There  can  be  no  doubt,  from  evidence  which 
will  be  considered  later,  that  the  lluid  is  in  a  constant  condi- 
tion of  motion  and  change. 

It  must  not  be  imagined  that  the  subarachnoid  space  is 
empty  save  for  the  lluid  which  it  contains.  Retween  the 
arachnoid  and  pia  pass  innumerable  fine  septa  which  sub- 
divide the  space  into  countless  loculi  all  comn;unicating  freely 
with  one  an.ithi-r.  These  j'.'ii'titions  are  clothed  l)y  the  en- 
dothelium which  lines  the  opposed  surfaces  of  the  pia  and 


i 


1 


ANATOMICAL   CONSIDERATIONS 


aradmoid.  The  result  is  that  the  subarachnoid  space  is  filled 
with  a  spongy  tissue  of  the  nature  of  areolar  tissue,  which  is 
continuous  with  the  spongy  tissues  already  described  as  form- 
ing the  chief  part  of  the  Pacchionian  lx>dies. 


^ 


THE  ARACHNOID  VILLI 

Tlic  following  account  is  largely  taken  from  the  very  full 
and  excellent  description  of  these  structures  given  in  Weed's 
monograph.  In  the  neighborho  d  of  the  great  sinuses,  es- 
jK'cially  the  superior  longitudinal  sinus,  finger-like  projections 
of  the  arachnoid  may  be  seen  to  penetrate  into  the  lumen  of 
the  sinus,  passing  through  the  dura  in  order  to  acciMnplish 
this,  'i'hese  projections  are  too  small  to  be  seen  bv  the 
naked  eye.  If  the  skull  cap  be  removed  in  tlu'  maimer  usual 
at  an  autopsy  they  will  be  completely  destroyed.  In  order 
to  demonstrate  them  the  brain  nmst  be  hardened  in  situ,  and 
the  cranial  vault  removed  jiiece  by  piece  with  the  greatest 
care. 

'i'he  villus  is  seen  in  most  characteristic  form  at  the  point 
where  a  cerebral  vein  enters  the  sinus.  The  vein  carries  a 
sleeve-like  prolongation  of  the  arachnoid  with  it,  the  vein 
itself  fonning  the  core  of  the  villus.  At  its  commencement 
the  villus  presents  a  fine  web-like  tissue  of  interlacing  strands 
similar  to  the  spongy  tissue  already  described  as  occurring  in 
the  subarachnoid  space.  There  is.  of  course,  an  external 
coxering  of  endothelial  cells.  Although  the  most  character- 
i-^tic  structure  is  seen  at  the  point  of  entrv  <  "  a  vein,  it  is  bv 
no  means  necessary  for  a'  villus  to  contain  a  vein.  Indeed 
ver\-  large  numbers  of  villi  arc  apparently  not  in  relation  to 
any  vein.  As  the  villus  approaches  the  sinus  its  central  struc- 
ture becomes  denser,  the  loose  network  disappears  and  its 
place  is  taken  by  a  myxomatous  material.  At  the  same  time 
in  certain  localities  other  than  the  superior  sinus,  notably  in 
the  region  of  the  cavernous  sinus,  the  endothelial  covering 
becomes  thickened,  the  cells  no  longer  form  a  single  laver, 
and  mav  be  piled  upon  one  another.  The  dura  mater  gives 
way  before  the  encroaching  villus,  which  finally  finds  itself 


lO        I'llYSIOI.OOV   AM)   I'ATIIOI.OCY   OF   Till;  Cl-RIBROSIMN' \L   FLUID 


projcctinrr  freely  into  the  sinus,  in  very  nuicli  the  >;iine  way 
that  tlie  chorionic  villi  project  iiitt)  the  Mood  >-inu.-.es  of  the 
pregnant  uterus. 

What,  tlien,  is  tiie  relationsliip  l>et\vcen  tlie  arachnoiil  villus 
and  the  racchionian  ^granulation  ?  Weed  is  of  o])inion  that 
the  granulation  is  merely  a  hypertrophic  villus,  tiuis  l)econi- 
ing  visihlc  to  the  naked  eye,  and  lie  regards  the  change  as  a 
pathological  one,  associated  with  the  increasing  age  of  the 
individual.  It  w  i'l  he  renienil)ercd  that  the  racchionian 
hodies  are  found  iKiiher  in  children  nor  in  the  lower  animals. 
The  arachnoid  villi,  on  the  other  hand,  are  met  with  at  all 
ages,  and  in  all  the  anini.als  inve-tigated,  namely  the  eat,  the 
dog,  and  the  monkey.  The  .'irachnnid  villus  ma}',  then,  he 
regarded  as  an  cxteu'-ion  of  the  ^uharachnoid  sp;ice  into  the 
cerelral  sinuses.  There  are  naturally  no  sji'ual  araclumid 
villi,  as  there  are  no  Mind  sinu-e--,  in  the  -pin.al  c;m;d. 

The  arachnoid  villi  are  not  the  only  examples  of  prolonga- 
titrus  of  the  suliar;icliiiiiid  ^p.ice.  .\s  the  cerehral  arteries 
pa>s  into  the  hrain  ^-uli-i.-ince  lliey  carry  with  them  a  fine 
sleeve-like  sheath  which  acconi]ian!es  the  ve- -el  until  it  he- 
comes  a  capillar\,  at  which  point  the  >he;ith  apparently  ends 
as  a  cul-de-sac,  hecoming  inc<irporatcd  with  the  vessel  wall. 
It  appears  again  arouufl  the  \ein-.  r.etween  the  sheath  and 
the  vessel  wall  there  is  a  s]i;Ke  tr.uersed  hy  tine  trahecukc 
much  after  the  fa-hinu  of  th'i-,'  already  de-crihed  as  occurring 
in  the  .suharachnoid  si)acc.  These  perivascular  space-  arc  not 
vi-ihle  in  tlie  normal  brain.  Only  under  >;i)cci;d  conditions 
can  thev  he  hrought  to  light.  The  s]iaccs,  fnvt  luentinued  hy 
Riihin  in  1N3S,  have  heen  fullv  de-crilK'd  hy  Mott  and  Weed. 
I'lOth  of  t'c-e  oh-ervers  produced  a  cor.dition  of  cerehr.'il 
aiKemia,  .Mi>tt  l>y  ligaturing  one  vertehral  and  hoth  cartoiil 
arteries,  Weeil  hv  e\-anguinatiiig  the  animal.  Under  these 
conditions  :i  vcrv  evident  sp;>ce  at  once  hi'coiue-  .apparent 
around  the  ve— els.  Th.at  this  sp,-ice  is  not  a  mere  artifact 
produced  li\-  collap>e  of  the  ve.--el  is  e\  idcncc'd  1)\'  the  prc-ence 
of  the  trahecuke  already  de-crihed.  The  e.\i>tencc  of  such 
a  .space  is  also  proved  hy  the  accumulation  within  i:   of  in- 


ANATOMICAL    CONSIDURATIONS 


II 


tlaniniatory  cells  —  lymphocytes  ami  plasma  cells  in  general 
paresis,  slccpini;  sickness,  and  acnte  poliomyelitis.  The  pen- 
vascular  spaces'  are  directly  continuous  with  the  subarachnoid 
space,  as  will  he  shown  when  the  origin  of  the  cerebrospinal 
lluid  comes  under  consideration. 

In  addition  to  the  perivascidar  spaces  it  is  also  possible  to 
demonstrate  similar  spaces  around  the  nerve  cells  in  experi- 
mentallv  produced  an:emia  of  the  brain.  The>e  perincuronic 
^paces  can  l)e  seen,  in  favorable  sections,  to  communicate  di- 
rectly with  the  perivascular  spaces,  and  tlius  e^•entually  with 
the  subarachnoi.l  space.  The  fact  that  the  nerve  cells  come 
in  this  manner  to  be  bathed  in  the  cerebrospinal  lluid  is  one 
the  importance  of  which  it  is  impos-ible  to  overestnuate. 

There  are  still  other  prolongations  of  d;e  subarachnoid 
space.  The  cranial  and  spin.al  nerves  as  they  issue  from  the 
brain  and  spinal  cord  carry  with  them  a  sac-like  prolongation 
of  tb.e  arachnoid  membrane  for  a  varyin;j;  distance.  These 
perineural  .sheaths  are  particularly  well  marked  in  the  case  of 
the  olfactory,  the  optic,  and  the  auditory  nerves. 

THE  SPINAL  SUBARACHNOID  SPACE 

Tn  the  spinal  canal  the  dura  mater  no  lou-er  presents  two 
layers.  The  outer  layer  which  acted  as  a  periosteum  for  the 
cranial  bones  has  now  disappeared.  The  vertebr.T  possess  a 
periosteum  of  their  own,  and  the  dura  mater  forms  a  loo.se 
linin,!,-  to  the  vertebral  canal,  the  intervening  space  bein?  oc- 
cupied by  areolar  tissue  and  a  few  veins. 

The  .arachnoid  and  jiia  mater  are  similar  in  every  respect 
t, .  those  of  the  cranial  cavity.  The  pia  terminates  as  a  definite 
membrane  at  the  point  where  the  cord  ends,  n.amely  the  lower 
l».r<ler  of  the  first  lumliar  vertebra.  In  the  child  the  cord 
ends  at  a  lower  level,  reachins:  as  far  as  the  b.vly  of  the  third 
lumbar  vertebra. 

The  arachnoiil  -ac  is  carried  down  as  far  as  the  first  piece 
of  the  sacrum,  and  contains  the  strands  of  the  cauda  equina 
in  addition  to  the  cerebrospinal  fluid.  It  is  into  {hi^  p.nrtion 
of  the  subarachnoid  space  that  a  needle  may  be  inserted  with 


12       I'HVSIOLOGY  ANU   I'ATIIOI.CXIY  OF  Till-    CKRIi nROSIMNAL  FLUIU 

perfect  safety   for  llic  purpose  of  uitlulraw inj;  a  sample  of 
tlie  cerebrospinal  tUud.      (li^-  -•) 


THE  VENTRICLES  OF  THE  BRAIN 

Tile  ventricles  of  the  brain  in  reality  form  one  lar^^e  cavilv, 
consistinjj  of  various  subdivisions  wliicb  coninuinicate  freely 
with  one  another.  'J'he  latenil  ventricles  o|K-n  by  the  furamina 
of  Monro  into  the  third  ventricle,  and  the  a(|ueduct  of  Svlvius 
esiablishes  a  direct  cotmection  between  the  third  and  fourth 
ventricles. 

In  the  roof  of  the  fnurth  ventricle  there  are  three  open- 
in.yfs,  a  central  opeiiinL;,  the  foramen  (>f  MaiL^endie.  and  two 
lateral  openinijs.  the  fi>rainina  i>i  I.UH-hka  or  Kuv  and  Ketzins. 
Althouf^h  the  actual  existence  of  these  openini^s  has  been 
called  in  (|nestion  in  recent  times  there  can  be  no  doubt  that  a 
free  communication  exists  beiween  the  lluid  in  the  fourth  ven- 
tricle ami  (hat  contained  in  l!ie  part  of  the  subarachnoid  space 
which  lies  in  immediate  relatioi.  to  the  medulla  and  cerebellum. 

The  third,  fourth,  and  lateral  ventricles  are  lined  throu!,di- 
out  by  the  cpcndyma,  a  layer  of  cubical  ei)ithelial  cells  ]\]v<^ 
upon  a  somewhat  den^e  and  niin-va<cular  fibrous  tissue.  The 
ependyma  subserves  the  pa-sive  function  of  linin-r  the  ven- 
tricular cavities,  and  probably,  in  health  at  least,  docs  not 
contribnte  to  nor  in  any  way  alter  the  composition  of  the 
cerelirospinal  fluid. 

I^injij  free  in  each  ventricle  there  are  two  hic;hlv  convoluted 
vr:  cnlar  tufts,  tb  choroid  plexuses.  These  i)roject  into  the 
ventricles  carrying'  before  them  the  linintj  ejiithelium  in  a  man- 
ner which  cannot  but  recall  the  tufts  of  Howman  in  the  kidney. 
They  are  produced  by  an  invajrination  of  the  pia  mater 
through  the  choroid  fissure.  The  epithelial  cells  coverinc;^  the 
tuft  are  differentiated  for  a  special  function,  just  as  in  the 
case  of  the  kidney.  They  become  lart^^er  and  more  columnar, 
and  in  many  rcs])ects  resemble  those  linin.i:;  the  alveoli  of  a 
sccretinj:^  inland. 

Cianjres  similar  to  those  seen  in  a  secretins^  gland  may  be 
observed  in  these  specialized  epithelial  cells  under  the  influ- 


.uiiilMr   innutnrr   nftillf    in    urailnmid    -ai .       I  <  rniii  ati^ 'ii   ,ii    iMinl 
at    lou'T   liordi-r   "I    tir^t    linnl  ar    MVU'Ta, 


1 


:'lF^^\f?^7 


ANATOMICAL   CONSIDFRATIONS 


13 


cncc  of  stimulants.     If  the  choroid  plexus  of  an  animal  l)c 
examined  immediately  after  the  admini>tration  of  ether  it  will 
lie   found   that  not  only  have  the  epithelial  cells  greatly   in- 
creased in  size,  but  a  dil'ferentiation  into  two  zones  has  taken 
place,   and  a  numher  ui   hyaline  droplets  may  Ix-   detected 
towards  the   free  margin.     I'urther,  some  of  the  cells  show 
these  changes  in  a  more  ma.ked  degree  than  others,  a  phe- 
nomenon also  to  l)e  observed  in  a  secreting  pland.     In  short, 
the  eiiithelial  cclU  covering  the  plexus  show  every  evidence 
of  being  in  a  state  of  active  secretion.     The  choroid  ])lexuscs 
of  tlie  various  ventricles  may,  therefore,  be  justly  reganled  as 
secreting  org.in<.      Mott  ci'iisidcrs  that  in  view  of  the  above 
f.-icts  it  is  now  jih-tilKiMe  to  speak  of  the  plexus  as  the  choroid 
gland.     The   importance   of   these   observations  on   structure 
becomes    apparent    when    the   (|uestion   of   the   origin   of    the 
cerelirospinal  iluid  comes  to  be  considered. 

REFERENCES 

Mott.  F.  W'.:  The  niivcr-Sh.irpcy  lectures  on  the  cerebrospinal 
iluid.     [..incet.  ii)i<),  ii.  July  J  auil  9. 

Weed.  E.  il.:  Studies  on  the  cerehrospinal  fluid  and  its  pathway. 
lour.  Mod.  Research,  lf)l-^  XXXE  No.  i. 


I  HAITI. K  111 


'iiii:  ()i>:i(ii\  Axi)  i)!:sii.\ Ai'io.x  oi"  riii'.  i'l.riD 


ORIGIN  OF  THE  CEREBROSPINAL  FLUID 

I'lndlc^s  (ll^l•ll>^ilPIl  and  iuiiir(i\i.r>y  has  taUiii  placo  ivt^ard- 
iiij,'  the  t>riL;iii  ol'  tlk'  circlini-pinal  lliiid.  and  the  tiiost  di\cr>e 
vit'\\>  have  at  dilkTciit  timi>  Irtii  cxprcsM'd.  (Iraduallv,  how- 
c'\cr,  lij;Iit  is  hi-iiiiiiiii^  to  iiiu'rt;e  I'nun  tlic  darkness,  and 
fad  to  take  the  plaie  ot'  theory.  I'litil  reeenth  it  was  as- 
sumed. iiatnrall\,  tlial  tlie  ihiitl  had  hni  a  single  source.  Once 
tlial  >ource  ua^  cKterinined  the  jirolilein  wduld  lie  solved. 
.\'o\v,  however,  it  i-,  reeojL;ni/ed  tiiat  there  ni.iv  l)e,  and  ])n>h- 
ahly  i>,  more  tlian  one  >oiirce.  This,  of  course,  achls  con- 
siderably to  the  diniciilties  of  the  proliletn,  hnt  in  l)iolo<,n-  it 
fre(|nentiy  lia])|)eiN  tliat  an  e.irly  simple  explanation  lias  to 
lie  repeatedly  inodillcd,  till  the  charm  of  its  orij^inal  sim- 
plicity is  entirely  lost.  We  must  he  prepared,  therefore,  for 
a  simil.ir  rcadjustmciU  in  our  views  concerniiiL,'  tlie  ori<rin  of 
the  cerebrospinal  lliiid. 

The  cerehruspinal  lUiid  is  contained  in  the  two  ,L;reat  cavities 
of  the  ventricular  system  and  the  subarachnoid  space.  Ila.s 
the  Ihiid  in  these  two  localities  a  common  orifjin,  or  does  a 
different  mechaniMu  come  into  play,  dependinj:^  on  anatomical 
differences  in  the  two  re,i,Mons? 

That  a  considerable  portion  of  the  fluid  is  produced  within 
the  cavity  of  the  ventricles  has  been  proved  incontestably. 
Such  i)roof  is  jKirtly  clinical,  partly  experimental  in  character. 
The  Condition  of  internal  hydroce])halus,  in  uiiich  the  ven- 
tricles become  distended  by  an  enormous  accumulation  of 
fhiid,  is  usually  associated  with  some  degree  of  obstruction  to 
tlic  outlets  ill  the  roof  of  tin.-  fourili  ventricle. 

If  the  afiueihict  of  Sylvius,  leading  from  the  third  ventricle, 

14 


I 


THE  ORIGIN    AND  DESTINATION   OF   THE    FLUID 


15 


111-  artificially  Mocked,  as  in  the  cNpcrimctital  tucthod  of 
DaiKly  and  iJlackfan.  a  mechanical  internal  hytlrucephaliis  will 
iiuarial)ly  ]k'  produced. 

Weed,  by  passinjj  a  cannula  tln'>Mj,'h  the  atiucduct  of  Syl- 
vius, was  able  to  withdraw  Ihii.l  di:cctly  from  the  ventricles, 
thus  cntirelv  climinatiii},'  the  surroiimlinu'  tissues.     After  the 


preliminary  increase  m 


tlow,  the  tluid  continued  for  several 


hours  to  drop  from  the  end  of  the  camnila  at  the  u>ual  rate 


The  only  structures  \\i 
:.ihlv  he  concernc( 


thin  the  ventricles  which  could  pos- 


\  with  the  production  of  the  Ihiid  arc  the 


r  the  ca\  itv.     Although 


itlv  suL'L'ested  as  the  sonrce 


choroid  plexus  ami  the  eiutidyma  lining' 
the  choroid  plexus  had  heen  fre<|nei 
of  the  fluid,  it  was  I'etit  and  Cirard  in  I'K^J  who  first  placed 
the  theory  on  a  firm  foundation.  These  observers  nia<lc  an 
extensive  and  thorouj;h  series  of  inve,-tij,'ations  upon  the  struc- 
ture of  the  choroid  plexus  in  different  classes  of  vertebrates, 
at  the  same  time  testins:  the  effect  of  hypersecretory  substances 
Slid  as  pilocarpine,  nmscarine.  and  ether.  They  found  that 
during  a  period  of  increased  production  of  iluid  the  epithelial 
cells  covering  the  jilcxus  showed  changes  very  similar  to  those 
obsiTved  in  an  ordinary  secreting  gland.  Mott,  following  a 
similar  line  of  investigation,  arrived  at  identical  results.  In 
a  later  paper  he  pointed  out  the  strong  similarity  between  the 
choroid  i)lexus  and  the  lachrymal  gl.and,  an<l  considers  that 
we  are  justified  in  speaking  of  the  :tn;cturc  a.,  the  choroid 

gland. 

Gushing  has  made  direct  observations  upon  the  choroid 
plexus  in  cases  where  a  porencephalic  cavity  communicated 
with  the  ventricles.  The  patients  were  under  ether  anrcs- 
thesia.  a  condition  well  calculated,  as  will  l)e  seen  presently, 
to  stimulate  the  production  of  fluid.  In  all  these  cases  he 
was  able  to  olwerve  droplets  of  fluid  exuding  from  the  sur- 
face (^f  the  choroid  ])lexus.  In  one  case  the  vessels  entering 
the  plexus  were  ligntured.  with  the  re^ilt  that  the  secretion  al- 
most immediatelv  ceased. 

■i'lie  most  biilliam  .-..ntHbutlini  is  that  of  Daivly.  who  in  a 
masterly  paper  proved  that  the  chor.Md  plexus  is  the  sole  source 


i6     rjiYsioi.ocY  AM)  i'.\Tii()i.()(,v  or  Tin:  ciRrnRosi'iNAi.  fluid 


of  the  tluid,  and  that  the  cpciHlyina  takes  no  part  in  its  produc- 
tidii.  l'«y  a  most  in<;ciiious  tccliiiic  lie  succeeded  in  hlockinjij 
tlic  foramen  of  Monro  on  rme  side  of  a  <lof;  s  hrain,  wliilst  on 
the  other  side  lie  tirst  removed  the  choroid  plexus  of  the  lateral 
ventricle,  leavinfj  the  cpeiidyma  intact,  and  then  Mocked  the 
foramen  of  Monro  on  that  side.  In  the  former  cue  the  ven- 
tricle hecame  f^reatly  distended  with  lluid.  a  condition  of  uni- 
lateral hydrocephalus,  lint  in  the  latter  it  hecame  shrunken  and 
collapsed,  containiuf;  not  a  drop  of  fluid.  althouf,di  still  lined  hy 
the  cpcndyma.  It  would  l)c  difficult  to  c^et  a  more  heautiful 
solution  of  an  a])parently  insolul)le  prohlem. 

Ts  the  tluid  in  the  suharachnoid  space  identical  with  that 
of  the  ventricles?  Docs  it  merely  represent  the  overflow  from 
the  ventricles  which  takes  places  throuc^h  the  npcninjjs  in  the 
roof  of  the  fourth  ventricle,  or  is  there  an  additional  source 
of  supniy  outside  the  ventricles?  It  certainly  is  not  identi- 
cal in  composition  with  ventricular  tluid.  It  contains  more 
albumin  and  less  sucjar.  Both  the  ,i,dohulin  and  the  comple- 
nient-ahsorhincc  substance  in  jjeiieral  paresis  are  more  alnind- 
ant  in  the  spinal  than  in  the  ventricular  fluid.  The  colora- 
tion of  the  fluid  which  occasionally  occurs  in  jaundice  is  .said 
to  be  more  marked  in  the  former  than  in  the  latter. 

The  fact  that  the  extraventricular  may  differ  con>iilcrably 
in  comiiosition  fnnn  the  intraventricular  tluid.  althoufjh 
.snq;f;;cstive.  is  by  no  means  conclusive  evidence  of  the  exist- 
ence of  some  mechanism  for  the  production  of  the  cerebro- 
spinal fluid  additional  to  that  of  the  \entrirles.  Much  more 
convincinc^  proof  is  afforded  by  the  observations  of  Dandy 
and  Rlackfan  on  a  case  of  internal  hydrocephalus  i  which 
there  was  complete  obstruction  to  tlie  outflow  from  the  ven- 
tricles. In  this  case.  althou,i;ironlv  five  cubic  centimeters  of 
fluid  could  be  withdrawn  by  lumliar  puncture,  it  was  pcissible 
in  a  comparati\-elv  slmrt  time  to  reco\er  another  similar  (|uan- 
tity.  .\s  this  fluid  could  not  ha\-e  conie  from  the  vcnfriclcs. 
it  must  have  oriijinated  from  some  extraventricular  source. 

If  there  is  an  additional  sr)urce  of  the  fluid  it  must  either 
be  the  endothelial  surface  of  the  walls  of  the  subarachnoid 


Tin;    ORIC.IN    ANT)   ni-STlNATION    OF   THE    FLUID 


17 


space,  or  tlic  perivascular  prolongations  of  that  space  which 
have  already  been  dcscrib<;d.  In  this  connection  the  ohstrva- 
tions  of  Spina  are  of  iniixjrtance.  This  observer  produced 
a  condition  of  high  intracranial  pressure  by  intravenous  in- 
jections of  suprarenal  extract.  On  exposing  the  arachnoid 
niatcr  he  noted  an  exudation  o'  clear  points  of  fluid  issuing 
from  its  surface.  I'roin  t'  ;.-  he  argued  that  the  direction  of 
the  How  was  probal)ly  tow  rds  and  not  a'vay  from  the  sub- 
arachnoid space. 

Th'.'  great  difficulty  in  ii.vtsugation:,  on  a  possible  dual 
s.nirce  of  the  cerebrospinal  tluid  is  the  separation  of  the 
ventricular  fn^ni  the  extraventricular  tluid.  Weed's  method 
of  overcoming  this  difticulty  by  introducing  a  cannula  along 
the  aiiueduct  of  Sylvius  into  the  third  ventricle  has  already 
i)een  described.  T.y  this  means  he  was  enabled  to  make  separ- 
ate observations  on  the  behavior  of  the  lluids  in  the  two  spaces 
under  different  conditions. 

Weed  has  further  attacl<ed  the  prolilem  by  means  of  his 
method  of  making  sul)arachnoid  injections  of  potassium 
lerna-vanidc,  bar.leiiin-  tl;c  Inain  in  silii  in  formalin  con- 
taining one  per  cent,  hydrocliloric  arid,  and  examining  for 
tlie  presence  of  granules  of  Prussian  blue.  He  found  that  al- 
th.nigh  the  granules  peiietralc.l  to  the  farthest  recesses  of  the 
perivascular  spaces,  there  was  no  evidence  of  their  passage 
into  the  vessels.  The  How  of  fluid  appears,  therefore,  to  take 
place  from  the  vessels  into  the  spaces,  ami  not  in  the  reverse 
direction  as  suggested  by  Mott. 

I'inally.  as  Cushing  has  poined  out,  in  cases  where  the  intra- 
cranial pressure  is  markedly  increased,  where  the  convolu- 
tions are  flattened  against  the  surface,  and  where,  therefore, 
the  exit  from  the  perivascular  spaces  tends  to  be  obstructed, 
the  spaces  are  found  to  be  distended  to  an  extent  never  seen 
in  health,  as  if  the  fluid  which  they  contained  was  being  pro- 
duced there  and  unable  to  escape.  There  seems  to  be  good 
reason,  therefore,  to  b-.lieve  that  the  fluid  in  the  subarachnoid 
sac  is  constantlv  being  augmented  by  additions  from  the  peri- 


vascular   si>acc-^ 


of    the    arachnniil    mater.     These   additions 


i8     riiYsioi.or.Y  and  i'atiioi.oc.v  of  tiih  cirebrosimn'al  fluid 

probably  carry  out  witli  them  the  ^)ro(hicts  of  neuronal 
i:ictal)oHsni,  o\vin<,r  to  the  clo<e  relation  which  exists  between 
the  perineuronal  and  peri\ascular  spaces,  so  that  a  difference 
between  the  subarachnoid  and  the  ventricular  tluids  is  to  be 
expected  rather  than  wondered  at. 

As  our  knowleds^e  of  tiie  cerebrospinal  fluid  becomes  greater 
it  will  possil)lv  be  found  that  various  parts  of  the  brain  and 
its  ap])endai,'es  make  characteristic  ad<litions  to  the  thiid. 
ru>hin,i;  and  (loetsch  have  already  advanced  evidence  to  show- 
that  the  secretion  of  the  po4erior  lobe  of  the  pituitary  t,dand 
is  i)oured  into  tlie  cerebrt)spinal  lluid.  and  a  recent  ca>e  of  my 
own  lends  support  to  this  view.  It  cannot  be  claimed,  how- 
ever, th.at  lhi>  matter  has  been  conclu>ively  proved. 

ABSORPTION  OF  THE  CEREBROSPINAL  FLUID 

'{"here  can  be  no  i|ue-tion  that  the  cerebrospinal  Huid  is  bein.s; 
continuallv  secreted.  N'ery  lar,L;e  ijuantities  may  be  with- 
drawn, and  be  replaced  within  a  short  space  of  time.  It  has 
been  estimated  from  observations  on  the  absorption  of  dyes 
from  the  subarachnoid  s])ace  and  subse(|uent  excretion  in  the 
urine  that  the  lluid  may  be  repl.iced  I'otu-  or  five  times  over 
(lurin,i(  twen;v-four  hotn-s.  .\s  the  tot  ■'  quantity  of  the  Huid 
in  man  is  i)rol)ably  somewhere  about  i  jo  cubic  centimeters  it 
is  evident  that  a  very  rajiid  and  extensive  absorption  of  fluid 
must  be  continn.illy  taking-  ])lace.  In  some  cases  of  fracture 
of  the  base  of  the  skull  l;irL;e  i|uanlities  of  tluid  have  been 
collected,  as  nuich  as  from  one  to  two  liters  sometimes  escap- 
in-,^  in  the  course  of  twenty-four  hours.  Cases  of  cerebro- 
spinal rhinorrhoa  or  e-cape  of  C(.rebros])inal  fluid  from  the 
nose  which  ficcasionally  occur  afford  strikin<:f  ocular  demon- 
stration of  this  conliinious  iiroduction  and  outllcnv.  In  a 
case  whicii  came  under  my  observation  some  years  aqo,  a 
case  in  whicli  direct  communication  h;i(l  been  established  be- 
tween the  cranial  and  nasal  cavities  owin;^  to  destruction  of  the 
interveninj:!;  structures  by  the  erodinji:  action  of  a  tumor,  a 
slow  f1(nv  of  fluid  took  place  from  the  nose  whenever  tlic 
patient  assuined  the  erect  posture.     This  flow  was  obser\eii 


ft . 


THE    ORIGIN    AND   DESTINATION    OF  THE    FLUID 


19 


I 

t: 


h 


over  a  period  of  many  months  and  the  total  amount  of  fluid 
lost  must  have  been  enormous.  By  what  channels,  under 
normal  conditions,  dn  s  tiiis  constantly  produced  fluid  make 
its  escape? 

The  major  part  of  the  fluid  undoubtedly  passes  into  the 
blood.  Leonard  Hill,  in  his  classical  work  on  the  circulation 
of  the  cerebrosi)inal  fluid,  found  that  when  saline  colored  with 
methylene  blue  was  injected  into  the  subarachnoid  space  the 
dye  appeared  in  the  bladder  and  stomach  in  from  ten  to  twenty 
minutes,  whereas  the  lymphatics  showed  no  trace  of  color  for 
a  much  longer  time.  Lcwanc'owsky  similarly  injected  potas- 
sium ferrocyanide  into  the  subarachnoid  space  and  regained  it 
from  the  urine  in  twenty  minutes.  Rut  the  problem  of  how 
the  fluid  gained  access  to  the  ccreliral  veins  still  remained 
to  be  solved. 

The  Pacchionian  bodies,  structures  .so  evident  when  even 
the  rough  methods  of  the  ordinary  post-mortem  examination 
are  employed,  were  naturally  the  first  to  attract  attention,  and 
at  first  sight  it  appeared  that  these  granulations  from  their 
anatomical  structure  were  well  ([ualified  to  act  as  a  filter  by 
means  of  which  the  fluid  could  escape  from  the  subarachnoid 
space  into  the  cerebral  sinuses.  When,  however,  it  was 
realized  that  the  structures  existed  in  neither  early  childhood 
nor  in  the  lower  animals  it  1)ecame  evident  that  some  other 
mechanism  must  be  looked  for.  Cushing  suggested  that 
valvular  openings  into  the  sinuses  might  exis^  through  which 
the  fluid  could  esca])e,  but  further  research  necessitated  an 
abandonment  of  this  view  also.  The  brilliant  experimental 
work  of  Weed  is  by  far  the  most  important  contribution  to 
the  sul)jcct  which  has  yet  been  made. 

The  technical  procedure  atlopted  by  Weed  has  already  l)een 
indicated.  I'v  hardening  the  brain  in  situ  in  a  fluid  contain- 
ing one  per  cent,  hydrochloric  acid  he  was  able  to  trace  the 
granules  of  Prussian  blue  resulting  from  a  preliminary  ante- 
mortem  subarachnoid  injection  of  potassium  ferrocyanide  and 
iron  ammonium  citrate  into  the  minutest  ramifications  of  the 
subarachnoid  space.     The  accuracy  with  which  it  was  possible 


20        IMlVSIOI.Or.V    WD    I'ATIIOI.OC.S-   OF   TMi;  CUREBROSIMNAL  FLUID 


to  fnlli)\v  tlie  course  of  tlie  injected  lluid  is  evident  from  a 
study  of  the  adniira!)le  plates  with  which  his  work  is  illus- 
trated. This  was  nnt  of  course  the  first  time  that  such  injec- 
tion methods  had  ken  employed.  Init  much  of  the  work  of 
pievious  ol)ser\ers  has  lieen  \itiated  hy  the  eni[>loyment  of 
ai, normally  hii^h  pressures  in  the  iirocess  of  injection.  With 
sucli  pressures  it  is  ([uite  possible  for  aI«iornial  channels  to 
he  opened  uj)  and  even  formed.  I'.y  usinj:^  pressures  only 
^lit^htly  ahove  that  of  the  cerel)ro>pinal  lluid,  or  still  better, 
by  the  method  of  re])lacenient  whereby  the  injected  lluid 
is  made  tn  take  the  place  of  an  C'lual  amount  of  tluid  which 
lias  been  withdrawn.  Weed  was  enabled  to  study  the  process 
ot  absor[)tiou  from  the  subarachnoid  sj)ace  under  normal 
Ciiuditions. 

'i'lie  outciime  i>f  the  work  wa->  to  prove  conclusively  the 
paramount  im]HiriaiK-e  nf  the  arachnoid  \illi  as  a  mechanism 
tor  the  pas^a^e  ol  the  cerelmispiual  lluid  from  the  sub- 
aracliiiiiid  >])ace  iiitu  the  ve!ii>u>  circulaiidu.  In  every  in- 
stance the  dark  blue  i^rannle-  could  be  traced  with  the  <4Tcatest 
ease  from  the  subarachnoid  ^pace  imo  the  villus-likc  processes 
which  project  iiUo  the  lumen  of  the  sinus,  and  eventually  into 
the  sinus  it -elf.  in  sotne  instances  the  t^fainiles  coid<l  be  de- 
tected in  their  passa^^'e  lietween  the  cells  coverinjj  the  villus. 
1  here  was  no  evidence  of  any  passage  between  the  cells.  Xor 
was  there  any  evidence  of  absorption  into  the  cerebral  capil- 
l.arie-.  'l"lie-e  ob-er\;!t!on-.  llieret'oro.  lend  no  sujiport  to  the 
\iew  advanced  ly  Mott  that  the  major  process  of  absorption 
t.'i'ces  place  into  the  capillaries  of  the  brain. 

Se\eral  factor-  favnr  the  llmv  of  lluid  from  the  sub- 
arachnoid >]i:ice  into  the  -itui-es.  The  pres-ure  in  the  veins 
is  lower,  so  that  the  lluid  tends  to  diffuse  tliroufjh  into  the 
blood.  There  i-,  in  f;ut,  a  coi:-t;n!t  ])roe<'-s  of  readjustment 
i^oiuij  on  between  production  and  absorption  of  the  fluid,  tl;e 
object  of  which  is  to  m.iintain  a  condition  of  accurate  bal- 
ance. I'pset  of  this  balance  is  a  jiathological  condition  which 
is  characteri/ed  by  the  immediate  api)earance  of  symptoms  of 
intracranial  disturbance.     The  blood  is  far  richer  in  crystal- 


THE    ORIGIN    AND   DliSTINATION    OF    THE    FLUID 


21 


Inuls  at.  colloids  llian  the  ccrclirospinal  tliiid,  and  this  is  a 
further  factor  in  deterniininjj;  the  flow  of  the  lluid  from  the 
stiliarachnoid  space  into  the  cerebral  sinuses. 

r.ut  aUhou,!;h  drainage  throu-h  the  arachnoid  villi  into  the 
threat  venous  sinuses  both  at  the  vertex  and  base  is  evidently 
of  the  first  importance,  it  does  not  follow  that  there  are  no 
other  means  of  escape.  The  fact  that  there  are  no  arachnoid 
villi  and  no  venous  sinuses  corres])ondinj,f  to  those  of  the 
cranium  to  be  found  in  the  spinal  canal  naturally  lead-  one 
to  look  for  some  other  possible  mechanism.  This  subsi-iiary 
mechanism  is  to  be  found  in  the  lymphatic  system. 

It  has  alreadv  been  pointed  out  that  definite  exteiiMons  of 
the  subarachnoid  s])ace  can  be  demonstrated  in  the  form  of 
tubular  sheaths  which  pass  for  a  varying  distance  alon^^  many 
of  the  cranial  and  spinal  nerves.  These  sheaths  are  especially 
well  developed  in  relation  to  the  olfactory,  the  optic,  and  the 
auditory  nerves.  'Ihese  sheaths  end  in  a  definite  cul-de-sac. 
beyond  which  injections  of  .granular  material  such  as  carbon 
cannot  pass.  I'.ut  when  ferrocyanide  solution  is  used  the  lym- 
phatics of  the  neck  will  be  found  to  be  deeply  stained.  A 
similar  result  was  obtained  bv  Leonard  1 1  ill  in  his  ori.tjinai 
observations  with  methylene  blue.  Tt  is  evident  then,  that 
absorption  can  take  ])lace  into  the  lymphatic  system,  but  this 
absorption  is  much  less  in  amount  than  that  into  the  venous 

simiscs. 

Tt  still  remains  to  be  shown  how  the  fluid  finds  its  way  from 
the  subarachnoid  cul-de-sac  into  the  lymphatics  of  the  neck. 
I'or  lonj,^  it  has  been  known  that  a  perineural  space  exists 
around  the  nerves  which  can  be  injected  from  the  subarach- 
noid space.  Cotu.uno  was  the  fir.-t  to  demonstrate  the  ex- 
istence of  this  space  by  injectini,^  it  with  air.  Tt  becomes  very 
evident  when  the  ferrocyanide  method  is  employed.  The  blue 
<,'ranules  of  ferric  ferrocyanide  can  be  traced  for  some  distance 
alono  the  nerve  in  the  i)erineural  sjiace.  Tliey  then  appear  to 
enter  a  somewhat  indefinite  open  reticular  tissue  from  which 
they  finallv  escape  into  the  Ivmpbatics  which  accompany  the 
nerves.     The.se  relations  can  best  be  studied  in  the  case  of  the 


22       PHYSIOLOGY  AND  PATHOLOGY  OK  THE  CEREBROSPINAL  FLUID 


olfactory  nerve,  where  the  various  channels  are  large  and  well 
defined,  but  similar  arrangements  exist  in  relation  to  the  other 
cranial  and  spinal  nerves. 

Although  this  accessory  path  is  of  relatively  little  im- 
portance in  comparison  with  that  into  the  venous  circulation, 
yet  in  the  case  of  the  spinal  subarachnoid  space  it  comes  to 
assume  a  position  of  greater  importance,  for  in  this  region,  as 
h.as  already  been  pointetl  out,  it  is  the  only  mechanism  pos- 
sible. In  all  of  the  spinal  nerves  absorption  from  the 
perineural  spaces  into  the  lymphatics  of  the  anterior  and 
posterior  nerve  roots  can  be  demonstrated  by  the  ferrocyanide 
replacement  method.  In  those  rare  cases  where  the  cr-^nial 
is  separated  from  the  spmal  subarachnoid  space,  and  in  which 
cerebrospinal  fluid  continues  to  be  secrctec!  into  the  perivas- 
cular sheaths,  the  lymphatic  system  of  drainage  must  be  re- 
garded as  of  considerable  importance. 

REFERFATES 

Boyd,  W. :  A  case  hearing  on  the  function  of  the  pituitary  body. 
Jour.  Am.  Med.  Assoc,  1917,  LWIII,  p.  in. 

Cushinp,  Harvey :  Studies  on  the  cerehrospinal  fluid  and  its  path- 
way.   Jour.  Med.  Research,  1912,  XXXI,  N'o.  i. 

Cufhinp.  Harvey,  and  Goetsch,  F.mil:  ConccrninR  the  secretion  of 
the  infundibular  lobe  of  tiie  pituitary  body  and  its  presence  in  the 
cerebrospinal  fluid.     Am.  Jour.   I'hysiol..   1910,  XXVII,  p.  fx3. 

Handy,  W.  E.  and  Black'an,  K.  D. :  An  experimental  and  clinical 
study  of  internal  hydrocephalus.  Jour.  Am.  Med.  Assn.  1913,  LXI, 
p.  2216. 

D.indy.  \V.  E.  and  Rlackfan.  K.  O. :  internal  hydrocephalus.  Am. 
Jour.  Dis.     Child.  Dec.   19 12.  p.  406. 

D.indy,  \V.  E. :  Expfrimental  hyrocephalus.  Ann.  Surp.,  1919, 
LXX,  p.  129. 

Hill,  1-eonanl:  riiysioloRv  and  patliolog:y  of  the  cerebral  circula- 
tion.    Churchill.     London.     i8()6. 

Lewandowsky :     Zcitschr  liii   Kliniscbc  Mcdicin,  XL,  p.  480. 

Petit,  .^.  and  Girard,  J. :  ?ur  la  fonctinn  secrotoire  et  la  ttiorpho- 
logie  des  plexus  choroidcs  dcs  veiitricules  latcraiix  du  systcme  ntrveux 
central.     Paris,  1912. 

Spina.  .'\.:  Experinicntcllor  P.ciiraK  zur  Kcnntniss  dor  Hyp'^remic 
des  Gehirns.     W  ion  .Mod.  151.  \><()X,  XXI.  Xos.  16  and  17.  p.  267. 

Weed,  L.  H.:     Loc.  cit. 


CHAPTER  IV 

CIRCULATIOX  OF  THE  FLUID 

Is  tlicrc  a  real  cirai:...i()n  of  the  fluid?     Is  any  movement 
tliat  may  take  place  merely  one  of  ebl)  and  flow,  or  does  the 
fluid  simply  lie  in  stagnant  pools  in  the  great  cisterns?     All 
the  analogies  of  biology  are  against  the  assumption  that  the 
fluid  is  in  a  stagnant  condition.     For  it  is  not  a  mere  means 
of  lubrication,  like  the  synovial  fluid  of  the  joints,  nor  is  it 
nothing  but  a  water  cushion  or  buflfer.  as  has  often  been  sug- 
gested.    It  has  an  active  part  to  play  in  the  economy  of  the 
central    nervous    system,    and    for   that    purpose    movement 
throughout  its  mass  is  essential.     Little  is  known  at  present 
regariling  the  direction  of  this  circulation  or  the  factors  which 
govern  it,  but  it  is  becoming  recognized  that  these  are  matters 
of  the  greatest  importance  in  connection  with  the  surgery  of 
the  brain  and  the  administration  of  therapeutic  remedies  by 
the   subarachnoid   route. 

The  cerebrospinal  fluid  may  in  this  connection  be  divided 
into  two  parts  —  the  part  above  the  tentorium  cerebelli  and 
the  part  below  that  membrane.     From  experimental  evidence 
there  can  be  little  doubt  that  substances  do  not  pass  readily 
from  the  lower  to  the  upper  chamber.     The  li  .id  from  the 
ventricles,  escaping  through  the  foramina  in  the  roof  of  the 
fourth  ventricle,  reaches  the  subarachnoid  space  in  the  sub- 
tentorial  region.     Fluids  injected  below  the  tentorium  oiily 
reach  the  cerebral  cortex  with  difficulty.     Thus  Goldmann,  in- 
jecting trypan  blue  in  the  lumbar  region,  found  the  greater 
part  of  the  nervous  system  stained  with  dye.  but  the  cerebral 
cortex  remained  unstained.     GoUa,  using  an  improved  technic, 
has  been  able  to  obtain  slight  staining  of  the  cortical  cells,  but 
in  a  much  less  intense  degree  than  in  the  rest  of  the  nervous 

23 


24     i'insi()i.(i(.\'  AM)  i'.\Tii(>i.o(,\  or  Tin:  ci:ri;iir()si'i\.\i.  fluid 

systLin.  lie  ciii])!t'y(,'(l  Cdlloidal  carlion,  ainl  allowed  a  few 
(lays  to  fhipx.'  iKiiire  killiiiL^'  tlic  animal.  I  lie  black  particles 
of  cailioii  ciitild  tluii  lie  deiiioii^trated  with  i^Tval  ease.  I'luids 
injected  alio\e  the  tentnriuni,  on  the  other  liand,  reached  every 
I)art  of  the  cerebral  cortex. 

.\s  a  re.-uJt  of  the^e  and  other  injectii)n  experiments  it  ap- 
pears to  be  established  that  substances  can  pass  with  com- 
parative ea-^e  from  the  >])inal  sac  to  the  Iowit  cranial  chamber, 
but  that  in  the  upptr  crani.d  chanilier  the  llow  i^  for  the  most 
|iart  fnnu  alxu'e  downward-.  The  imjiortance  of  the>e  ob- 
servations i-  obviiiu-.  and  will  be  referred  to  a.qain  when  <lis- 
cu->inL;  the  admini-ir.itinu  of  tiierapeuiic  reniedio  by  the  in- 
traspinal route.  TIh y  ma\  ser\e  in  jiart  to  explain  the  ef- 
ficacy of  lumbar  injectiou-  of  saU.-ir-.ini^ed  serum  in  tabes 
dor--alis.  and  the  ninch  nioro  I'i-.-ippointini;'  re-ult>  of  the  same 
treatment  in  j^reneral  pare-is. 

It  is  a  littk  dil'licult  to  nnde'-^tand  where  the  downward  How 
from  the  cirebnu  corttx  ori;;inates,  seeing  that  the  ventricular 
lluid  e~ca]n's  iu  the  -ubtentori.al  ret^ion.  .\  ])robable  ex])lana- 
tion  is  to  be  found  in  the  acce^-ory  intramedullary  source  of 
supi)ly  provided  by  the  perivascular  spaces.  This  Ihu'd  streams 
downward  to  min::,de  with  the  Ihiid  from  the  ventricles  in  the 
basal  cisterns.  It  nni-t  fmther  be  remembered  that  under 
normal  conditions  the  amount  of  lluid  in  the  subarachnoid 
space  above  the  tentorium  is  very  small. 

It  has  been  su,i;i;ested  by  Kramer  that  there  may  be  an 
ascendint;  current  in  the  central  canal  of  the  cord.  Injections 
of  meth}lene  blue  were  found  to  pass  into  tlie  canal  by  a 
caudal  nietap(jre,  and  to  ascend  with  the  canal.  The  matter 
must  still  be  consiilered  sub  jiulici'.  however,  for  the  work  of 
subsequent  observers  has  not  substantiated  thi.s  liypothesis. 


FACTORS  INFLUENCING  THE  FLOW  OF  THE 
CEREBROSPINAL  FLUID 

■  '  '■  '' 
If  the  choroid  plexus  is  in  reality  to  be  regarded  a.s  a  se- 
cretory gland,  it  i.s  to  be  expected  that  some  .sub.stances  will 
exercise  a  stimulating  effect  upon  it.     Tn  investigating  prob- 


CIRCULATION    OI"   Till:    Fl.t'II) 


25 


k'ins  omnectcd  with  tlie  llnw  of  tlu'  Hiiid  and  the  allied  suh- 
jtTt  of  cerehrospiiial  pressure,  it  i-  lucessary  to  hear  in  mind 
tl'.at  several  different  factors  may  l>e  involved  in  any  \;i\m 
chan.i^e.  I'nie-s  this  he  done  i|uite  ermneou^  conclusions  may 
he  arri\ed  at.  1'or  an  increased  llou  or  a  heit,dUened  pressure 
mi;,ht  he  due  to  increased  ])roduction  (>f  llnid.  or  to  a  rise  of 
arterial  or  venous  ])ressure. 

Of  the  \arious  worker--  in  thi--  field  l)i\ou  and  Ilallilntrton 
have  made  the  most  uoiaMe  coutrihution.      \'>y  takiii!;'  -innil- 
taneous  records  of  the  cerehro-jjiual  pressure  and  the  pressure 
in   the   f,'reat    sinuses   they    were  ahle  to  di-tin,i;uish   rises  of 
pressure  of  vascular  ori-in  imm  those  due  to  increased  sccrc- 
tiou  of  tluid.     'i'l'.ey  fomid  that  ceriain  sulistances  act  as  true 
cerehral   lymphaRoj^ucs.     Of  these,  tlion-   which  had  a  truly 
siiecific  action  were  extract^  i.f  choroid  ])ieNUS  and  hrain  tissue. 
Norma!  cerehror^innal  Ihiid  produced  no  effect,  hut  intravenous 
inii'ctions  of  lluid  from  ca-L<  of  'general  p;:r;dysis  and  cerehral 
di-inte,qration  were  followed  hy  an  increased  llow.     They  su^- 
;,^est  that  a  hormone  may  he  proiUiced  hy  the  hrain  suhstance, 
.and  carried  to  the  choroid  plexus,  where  it  stinmlates  the  epi- 
thelial cells,     'jhis  would  exjilain  the  presence  of  an  excitant 
in  the  tluid  in  cases  of  cerehral  deqcueration. 

In  addition  to  these  specific  stimulants  they  found  other 
factors  of  i,^reat  impori.uice.  Of  these  the  chief  was  the 
presence  of  excess  of  cariion  dioxide  in  the  hlood.  '[he  ani- 
mals were  kept  under  artificial  respiration  durin.^:  the  ex- 
l)eriments,  and  the  mon  t  that  a  deficiency  of  oxygen  or  an 
excess  of  carhou  dioxide  was  ])ermiited  in  the  inspired  air, 
the  fluid  at  once  hej^an  to  llow  freely  from  the  cannula.  If 
an.-e.sthetics  such  as  chloroform  or  ether,  or  drugs  such  as 
pilocarpine  or  amyl  nitrite,  he  employed,  the  result  is  the  same. 
In  such  experiments,  therefore,  it  is  advisahlc  to  use  morphine 
and  urethane  as  an  ansesthetic.  comhined  with  the  use  of  ar- 
tificial respiration. 

This  i)henoinenon  of  increased  fiow  of  fiuid  resulting  from 
ex-ces.'^  of  carhon  dioxide  in  the  hlood  is  readily  imderstood. 
The  cerehrosninal  fiuid  is  one  of  the  means  of  producing  a 


i  I 


26        IMIVSIOUKJY   AND   I'ATIIOI.CKJY   OK   Till:   ChRinROSIMNAI-   FI.VID 

rapid  excretion  of  carlnm  dioxide  and  when  the  carlH)n  dioxide 
in  the  l)I(Hid  rises  alM)\e  normal  it  is  natural  that  the  process  of 
excretion  should  ho  hastened.  .\nalof;ies  may  Ik.-  found  in  the 
increased  flow  of  urine  foUowinj;  injection  of  urea,  and  the 
cholagogue  action  of  hile  salts. 

The  conditions  which  favor  an  iiurca^cd  How  of  iluiil  also 
tend  to  produce  a  rise  of  cerebrospinal  pressure,  i-'or  this 
pressure  is  largely  independent  of  the  arterial  or  \enous  pres- 
sure. The  factors  which  intluence  it  are  the  raie  of  produc- 
tion and  the  rate  of  absorption. 

PERMEABILITY  OF  THE  MEMBRANES 

Manv  sulistances  pass  with  ease  from  the  cerehrospinal  fluid 
into  tlie  veins.  Imt  very  few  can  pa-s  from  the  Mood  into 
the  fluid.  The  epithelium  of  tlie  choroid  plexus  presents  an 
impenetralile  harrier  to  the  vast  majority  of  substances  which 
trv  to  make  this  passa^^-.  ]'y  this  rii^'id  censorship  it  protects 
the  delicate  nervous  structures  from  the  action  of  harmful 
substances.  Toxins  ate  excluded.  Tetamis  toxin  injected 
subcutaneously  does  not  ap^uar  in  the  fluid.  The  s|;ecifk 
agglutinin  foimd  in  typhoid  fever  is  also  absent.  Intravcnou.s 
injections  of  dyes  fail  to  reach  the  spinal  fluid.  Crystalline 
substances  taken  by  the  mouth  or  injected  into  the  veins  can- 
not Ix.'  recovered  from  the  fluid.  The  importance  of  these 
f.icts  from  the  therapeutic  standpoint  is  of  course  obvious. 

The  exclusiveness  of  the  choroid  plexus  is  not  (|uite  com- 
plete. Alcohol,  chlorofomi,  and  acetone  arc  allowed  ready 
passage,  and  Oowe  has  shown  that  urotropin  administered 
internally  can  be  recovered  from  tlie  cerebrospinal  fluid.  As 
a  result  of  this  last  observation  it  has  become  the  custom  to 
give  urotropin  as  an  antiseptic  in  cases  of  meningitis.  Thi.s 
is  one  of  the  instances,  so  often  provided  by  the  history  of 
medicine,  of  an  extensive  practice  being  built  up  on  the  slender- 
est foundation.  For  the  drug  api>ears  in  the  fluid  in  quan- 
tities so  small  that  it  can  have  no  effect  in  staying  the  progress 
of  a  ca.sc  of  acute  mc^i^,^ilis.  I'urther  Dixon  and  Ilal'ilmrton 
and  other  workers  have   failed  to  detect  any  trace  of  for- 


CIRCULATION    OF    TIIK    FIX' lU 


27 


.ualclchvde.  to  ul,ich  the  anli>c,.lic  acti..,,  ..f  uroin.inn  .s  .luc 
Any  small  traces  of  urotropin.  however,  which  nuiy  be  present 
may  exert  a  very  nseful  prophylactic  intlncme.  an.l  ren-ler  the 
flui.l  unsuitable  for  the  growth  of  a  few  inva-huR  organisms, 
l.'or  this  reason  it  is  well  worth  while  to  ^nve  prophylactic 
doses  of  the  <lruK  in  cases  of  fracture  of  the  skull.  wouu.K  of 
the  head,  an.l  before  oiK-ratiug  on  eases  of  acute  nu.ldle  ear 

inllanimation.  ,i     1 1      i  »,. 

Formidable  as  is  the  obstacle  to  passa;.^e  from  the  blood  to 
the  spinal  iluid.  mauv  substances  can  pa>s  u,  the  opposite 
directum  with  remarkable  ea>e  an-l  rapidity,  e'rystalhue  siib- 
stances  may  be  absorlH.-.!  and  produce  their  characteristic  ettect 
almost  as  cpucklv  as  when  injected  .brectly  into  the  veins. 
Thus  Dixon  and  Halliburton  have  shown  that  .atropm  in- 
jected into  the  subcerebcllar  cislerna  of  a  .lo.^^  will  pro.uce 
vagal  paralvsis  in  a  minute,  whilst  with  a.lrenahn  the  latent 
period  may  be  as  short  as  ten  seconds.      I'.tuitary  extract  is 

also  rapidlv  absorK-d.  .       ■    .1 

(•  vcn  more  remarkable  than  the  rapidity  of  absorption  is  the 
amount  of  fluid  which  can  Ik,-  absorbe.l.     Anythui-  up  to  a 
liter  of  noniial  saline  may  be  run  into  the  sulK.-erelellar  cis- 
lerna of  a  dog.  and  be  abs..rbed  in  the  space  ol  one  or  two 
hours      This  enormous   power  of   absorption   l)ecomes  com- 
prehensible, however,  when  the  amount  of  cerebrospinal  fluid 
secreted  is  considered.     From  observati.nis  on  the  absorption 
and  excretion  in  the  urine  of  phenolsulphonephthalein  injected 
into  the  subarachnoid  space  it  appears  probable  that  the  entire 
<,uantity  of  cerebrospinal   fluid   is  completely  renewed  about 
every  four  hours.     Grantiiii;  that  the  average  volume  ot  fluid 
is  somewhere  alx)Ut  one  hundred  or  one  hundred  and  twenty 
cubic  centimeters,  this  would  give  a  total  absoq^tion  of  between 
six  and  seven  hundred  cubic  centimeters  in  the  course  of 
twenty-four  hours.     The  greater  part  of  this  absorption  takes 
place  from  the  cranial  subarachnoid  space,  comparatively  little 
occurring  in  the  spinal  part  of  the  space.     This  again  is  a  poiut 
for  the  therapeutist  to  bear  in  mind. 
Colloids,  on  the  other  hand,  are  absorbed  with  great  dif- 


jS     I'1i\M()i.o(;v  .\\i>  r\rii()i.(H.\  op  thi  ci  ri  urom'in ai.  i  i.i  id 

liiiilly  or  riot  at  all.  \\itti'>  pciitoin-  and  a  loreij;n  siriim  arc 
protein,  ilu'  prf>(,iu\-  of  wliirli  in  tlii-  Mood  >trf:iin  can  Ik- 
rooiLrni/c-il  hy  tluir  cliaraili-ri^tif  pliy^iolo^iial  action. 
Xii'liiT  oi'  ilu-si-  ^nli^lanci's  can  pas^  Itoin  ilic  (crclim^pinal 
lluid  into  till-  Mood.  I'lic  rca-on  for  tlii>  dirtVrnuc  in  Ik- 
liavior  inidoiihlcdly  dcjHnd--  on  tlic  -i/i-  ,,f  tin-  inoIccuK'.  'I'lic 
lar!;c--.i/'cd  inolicnlo  of  tlic  colloid  arc  denied  pa^-a.^c.  'i'lii, 
eltectualls  (livposi>  of  any  theory  of  \al\nl.ir  openinj;,  from 
tile  ^uliaracimoid  ^pace  into  llie  cereliral  Hini>e>. 

Ki  |-i:ki:n-cf..s 

<  Miwf.  S.  I.:  (  »n  till'  cxi-rctiMn  of  lioNanirili)  Un.in'in  (  niipiiii]iiii ) 
ill  the  cerelirciviiiiial  lluid  and  its  tliciMiiciilic  valiu'  in  iiu'niiii:itis. 
liiill.     Jiilitis   Il"|ikins   l[(i^[).    i<)(x),   \\.   p.    idj. 

Dixon.  W.  i:.  and  I  lallilmrion,  W.  |). :  'fhc  ccrclitospin.il  tlui.l. 
Jour.  i'livMoI.  101  V  Xl.Xdl,  |.  ji;:  h)!}.  .Xl.XIir,  p.  i.-S;  11)14,  ,!„. 
p.  .^17:   11)1'''.  F,.  p.   ic).^. 

Kr.iniiT.  .»-;.  I'  :  Tlir  eirciilalion  of  ilie  ccrdiro^jiinal  fluid.  N'cw 
'S'ork  Mcil.  Jnnr.  njij,  X(.'\',  p.  ^^j. 


CHAPTER  V 

I  III-.  llXtTIOXS  OFTlil'.CI'.UI'I'.UOSI'IXAL  ILLID 

'I'Ik'  i-iivlirnspiiial  fluid  imist  Iiavc  some  important  fuiution 
to  perform.      Tliat  which  is  usually  assigned  to  it  is  a  purely  — 
or  at   least   mainly  —  mechanical  one.     It  is  compared  to  a 
water  jacket,   an  all-perva<linj,'  medium   which  supports  and 
protects  the  central  nervous  sy>tem,  shielding'  it  from  the  rude 
shocks  and  blows  of  the  outsiile  world,  adaptini,'  itself  to  the 
var\in^i,'  conditions  within  the  cranial  cavity,  accommodating 
the  lirain  in  the  matter  of  -pace,  ehhing  and  Mowing  in  respimse 
to  tlie  demaniN  i>f  the  clianging  \olume  of  Mood  in  the  c.-rebral 
vessels,  and   in  general  subserving  the  useful   tht)ugh  some- 
what humble  function  of  a  stopper-up  of  gaps.     lUit  is  it  lor 
this  .-done  that  the  Huid  exists?     Is  it  for  this  that  there  has 
been  created  the  complex  system  of  the  ventricles,  the  great 
.stretch  of  the  suljarachnoid  sjjace  with  its  cistems  and  lakes, 
and  the  wonderful  prolongaticms  of  that  .space  deep  d(3wn  into 
the  substance  of  the  brain  bringing  even  the  individual  nerve 
cells  into  intimate  connection  with  the  Ihiid?     It  seems  alwut 
as  reasonable  to  suppose  that  the  blood  fills  the  vessels  that 
they  may  Ix;  distended  to  the  proper  extent,  or  that  the  chief 
function  of  the  circulation  is  to  warm  the  Ixxly.     The  whole 
uni(iue  constitution  of  the  lUtid,— the  sugar  for  puriuises  of 
metabolism,  the  high  content  of  carlxju  dioxide,  the  peculiar 
changes  in  the  fluid  in  pathological  states,— cries  out  against 
such  a  supposiiion.     No  doubt  the  fluid  plays  an  important 
p.irt  in  the  mechanics  of  the  cranial  cavity,  it  must  furnish 
a   ctjuvenient    mechanism    for   compensating   changes    in    the 
cerebral  voliune,  but  in  addition  it  must  surely  be  concerned 
w^itl:  the  mctaboli-ni  of  nervous  tissue. 

The  cerebrospinal  fluid  doubtless  has  many  uses.     Encasing 

29 


30        PIlVSIOI.or.Y  AM)   I'.ATK     locY  OF  THE  CFREBROSl'I VAL  FLUID 


ft 


and  cnvelDpiiif:;  a-;  it  doc-  llie  wliolo  central  nervous  system, 
it  cannnt  Init  act  ,i>  a  i)n>tcctioii  against  sudden  shocks.  'Hie 
inodulla  ohlimj^ata,  tlie  most  delicate  and  vital  part  of  the 
lirain,  is  so  surrounded  by  tiic  cistcrna  nias^na  and  the  cisterna 
pontis  that  it  may  he  rct;arded  as  lyint,^  in  a  water  hath.  The 
cranird  cavity  is  hounded  ly  ri^id  and  inexpandahlc  Avails, 
'i'lie  only  way  in  whicli  the  hrain  can  ])ossil>Iy  expand  is  for 
the  cerclimspinal  lluid  to  llow  out  of  the  cranial  eavitv  into 
the  spinal  canal.  That  there  is  need  for  such  a  inechanistn  is 
easily  pn)ve(l  hy  a  few  oI)>ervations  on  the  chancres  which 
may  iKcur  in  cerebrospinal  |)ressure.  Such  an  act  as  cough- 
ing; or  cryini,'  at  once  causes  the  fluid  to  tU)w  out  of  the  skull. 
In  such  conditions  as  cerdiral  cons^estion  or  ledema  the  de- 
mand I'or  such  a  lucchanism  is  still  more  evident. 

Owins;  to  the  ])eculi;>.'-  constitution  of  the  cerebrospinal 
ihiid  and  tlie  remarkable  selective  action  of  the  choroid  plexus, 
it  is  ])ossiblc  that  the  lluid  ])Iays  an  imi)ortant  part  in  protect- 
in;;  the  nervous  tissue  from  the  action  of  harmful  substances 
circulating;-  in  the  blood.  It  has  been  shown  that  substances 
such  as  barium  chloride,  which  prove  fatal  when  injected  into 
the  spinal  canal,  may  circulate  in  the  blood  in  a  concentration 
a  thousand  times  greater  before  they  ])ro<luce  injury  to  the 
I)raiu.  Saharsan  can  be  given  intravenously  in  large  doses 
without  producing  any  toxic  action  on  the  brain,  hut  even 
nu'nute  (|uamities  may  have  a  fatal  etYect  when  injected  into 
the  spinal  canal,  liacterial  and  other  toxins  are  in  a  similar 
manner  excluded  from  reaching  the  nervous  tissues. 

L'seful  and  important  as  these  functions  must  be,  there  can 
be  little  doubt  that  the  fluid  is  alxjve  all  concerned  with  the 
nutrition  of  and  the  eliiuination  of  waste  products  from  the 
elements  of  ilie  central  nervous  system.  It  is  for  this  reason 
that  the  carl)on  dioxide  content  of  the  fluid  is  so  high.  It  is 
probably  for  this  reason  that  the  composition  of  the  fluid  may 
vary  materially  in  dif¥erent  places.  The  composition  of  the 
fluid  is  itself  highly  suggestive.  It  contains  a  small  quantity 
of  sugar  and  a  trace  of  albuiuin.  The  sugar  provides  the 
energy  needed  in  the  metabolism  of  the  nerve  cells  and  fillers, 


THE    FUNCTIONS   OF   THE   CEREBROSPINAL    FLUID 


31 


whilst  the  albumin  provides  nourishment  for  these  structures. 
It  is  true  that  the  alljiimin  content  is  low,  but  it  is  probably 
sufficient  for  the  purpose,  for  the  wear  and  tear  of  the  nervous 
tissue  is  not  great.  Halliburton  has  pointed  out  the  remark- 
able similarity  between  the  cerebrospinal  lluid  and  Locke's 
physiological  saline  solution,  which  contains  0.9  per  cent, 
sodium  chloride  and  a  small  quantity  of  glucose.  Locke's 
fluid  is  known  to  be  an  almost  ideal  fluid  for  nourishing  the 
tissues  and  removing  the  products  of  metabolism.  Mott  es- 
timates that  the  carbon  dioxide  content  of  the  fluid  is  over 
fifty  per  cent.  This  again  strongly  suggests  that  the  fluid 
plays  the  part  of  the  lymph  of  the  brain.  .\t  the  present  stage 
of  our  knowledge  the  matter  is  not  susceptible  of  proof,  but 
every  analogy  and  prolxibility  points  to  the  fact  that  the  fluid 
has  a  metalxjlic  as  well  as  a  mechanical  function  to  pcrfonn. 

THE  NATURE  OF  THE  CEREBROSPINAL  FLUID 

Two  main  views  have  been  advanced  as  to  the  nature  of 
the  fluid.  On  the  one  hand  it  has  been  held  that  the  fluid  is 
a  transudate,  passing  out  from  the  blood  vessels  by  the  physical 
process  of  transfusion.  Against  this  conception  it  is  possible 
to  bring  a  formidable  array  of  facts.  The  fluid  bears  no 
resemblance  in  composition  to  that  of  other  transudates  oc- 
curring in  the  body,  of  which  the  most  important  is  lymph. 
Although  the  fluid  has  been  described  by  Mott  as  a  lymph  of 
the  brnin,  it  differs  from  lymph  in  one  important  particular. 
The  blood  scrum  contains  about  6.5  per  cent,  of  albuminous 
matter,  and  of  this  over  4.5  per  cent,  appears  in  the  l\mph. 
The  process  of  filtration  through  the  walls  of  the  capillaries 
is  accordingly  a  coarse  one,  for  even  the  large  colloid  mole- 
cules of  albumin  are  allowed  to  pass.  In  the  cerebrospinal 
fluid,  however,  the  protein  is  only  present  to  the  extent  of 
.018  per  cent.  It  is  evident  that  here  we  are  not  dealing  with 
a  .simple  transudation  uninfluenced  by  other  factors. 

On  the  other  hand  tlu  fluid  has  l>ecn  regarded  as  a  secre- 
tion produced  by  the  choroid  plexus  or  choroid  gland.  I'or 
this  view,  which  is  at  present  the  popular  one,  there  is  much  to 


i2        PHYSIOLOGY   AND   TATHOLOCV  OF  Till-    CKRIiBROSI'IN'AL  FLUID 


f, 


be  sai'i.  Certainly  tlie  cliomii'  plexus  is  intimately  concerned 
witli  the  prodnction  of  the  fluid.  1'ut  are  we  justified  in  using 
the  term  secreti(Mi  in  this  sense?  In  the  secretions  of  the 
hody  such  as  the  sweat,  the  I)ile,  the  milk,  and  tiie  saliva, 
there  is  somethiufj;  added  to  the  fltn'd  secreted,  some  distinctive 
component  tlie  result  of  the  vita!  activity  of  the  cells  enjjap[ed 
in  the  secretory  jirocess.  What  is  there  of  this  nature  to 
which  we  can  ])oint  in  the  case  of  the  cerebrospinal  fluid? 
Xothintj  is  added  or  synthetised.  It  is  merely  a  case  of  sub- 
stances beinj:^  held  back. 

Under  these  circumstances  the  most  reasonable  hypothesis 
.seems  to  In?  that  of  Mestrezat,  who  re,c:ards  the  fluid  as  an 
"elective  filtration."  the  result  of  dialysation  through  a  mem- 
brane which  has  the  power  of  holdin.^f  back  almost  all  sub- 
stances other  than  those  immediately  nccessarv  for  the  func- 
tioning; of  the  nervous  tissue.  In  this  wav  the  threat  class  of 
albuminoid  toxins  are  forbidden  access  to  the  nerve  centers. 
Me-trezat  classes  the  cerebrospinal  fluid  alon,;::  with  the 
a(|ueons  humor  of  the  eye  and  the  endolymph  of  the  internal 
car  as  beloncfinf;  to  one  family  which  he  nanu's  the  neuro- 
protcctors.  It  must  be  admitted,  however,  that  it  is  dilTicult 
to  reconcile  with  this  view  the  fact  that  the  cerebrospinal  pres- 
sure may  be  increased  without  a  correspondin,";  and  causative 
increase  in  the  pressure  within  the  l)lood  ve-;sels.  The  process 
may  be  one  of  filtnition  in  the  sense  that  certain  substances  are 
held  back,  but  the  term  is  apt  to  create  a  false  impression, 
for.  under  certain  circumstances  at  least,  the  choroid.il  epi- 
thelium plays  a  much  more  active  part  than  that  of  a  mere 
restrainer.  I'lider  normal  conditions  the  process  is  probablv 
one  of  filtration,  but  when  the  choroid  yland  is  stimul.ited  to 
activity  the  process  becomes  one  of  active  secretion. 


REFERF.XCES 


TTalliluutoti.  W.  D. ;  Tlic  possilik-  functions  of  the  CiTclirns])inal 
flnid.     P.rit.  Mcil.  Jmir.,  \q]C\  IT.  p.  Goc)- 

Mcstrczat:  I.c  liquidc  ceplialo-racliidicn  normal  ct  patliologinue 
Paris,  191;;. 


CHAPTER  VI 
PRESSURK  OF  THE  CEREBROSPINAL  FLUID 

It  is  seldom  tiiat  in  clinical  reports  we  find  an  attempt  to 
detennine  the  pressure  of  the  spinal  fluid  with  any  dej^ree 
of  accuracy.  As  a  rule  we  have  to  l)e  content  with  the  in- 
formation that  the  pressure  is  "  normal "  or  "  raised." 
Often  no  reference  of  any  kind  is  made  to  it.  And  yet  from 
the  point  of  view  of  the  physician  and  surgeon  a  knowledge 
of  the  pressure  within  the  cranial  cavity  and  of  the  conditions 
which  may  produce  heightening  of  that  pressure  is  of  the 
greatest  importance.  For  it  is  becoming  increasingly  recog- 
nized that  increased  or  decreased  intracranial  pressure  may 
he  the  chief  factor  in  producing  cerebral  symptoms  in  widely 
differing  affections.  It  has  long  been  known  that  the  head- 
ache, vomiting,  and  optic  neuritis  of  cerebral  tumor  are  di- 
rectly due  to  high  intracranial  pressure,  but  only  recently  has 
it  been  realized  that  the  convulsions  in  eclampsia,  the  coma 
in  unemia,  and  the  tinnitus  and  giddiness  in  certain  affections 
of  the  interna!  ear  may  be  associated  with  a  similar  condition. 

Many  estimations  of  the  normal  cerebrospinal  pressure  have 
been  made  at  different  times,  and  the  results  obtained  vary  to 
an  extraordinary  degree,  such  widely  divergent  figures  as  50 
millimeters  and  450  millimeters  of  water  having  been  given. 
The  reason  for  this  enormous  difference  of  opinion  is  no  doubt 
twofold.  On  the  one  hand  no  standard  instrument  has  been 
agreed  upon.  Each  observer  manufactures  or  improvises  one 
for  himself,  so  that  it  can  hardly  be  wondered  that  the  results 
vary.  On  the  other  hand  the  inllucnce  of  incidental  factors 
on  the  cerebrospinal  pressure  has  not  been  sufficiently  realized. 
Of  these  factors  the  two  most  important  are  gravity  and 
venous  pressure.     A  change  from  the  horizontal  to  the  erect 

33 


34       PHYSIOLOGY  AND   I'ATIIOLOGV  OF  THE  CEREBROSPINAL  FLUID 


position  will  often  produce  a  very  marked  change  in  the 
cerebrospinal  pressure.  Anything  which  causes  engorgement 
of  the  '-("rehral  veins  tends  to  raise  the  cerebrospinal  pressure. 
I'ven  the  act  of  coughing  and  the  movements  of  respiration 
affect  that  pressure.      (Fig.  3.) 

Of  the  various  methods  of  estimating  the  cerebrospinal 
l)ressure,  the  simplest  and  the  best  adapted  for  clinical  pur- 
poses is  that  of  Cassidy  and  Page.  The  apparatus  consists  of 
a  lumbar  jnnuture  needle  provided  with  a  cock  at  the  blunt 
end,  and  rubber  tubing  a  meter  in  length,  to  one  end  of  which 
is  attached  a  tapi)ed  nozzle  which  fits  into  the  needle,  and  to 
the  other  end  a  simple  glass  tube  18  cm.  long  and  1.5  cm. 
in  diameter.  The  patient  lies  in  the  recumbent  posture,  great 
care  being  taken  that  the  cerebrospinal  axis  is  horizontal. 
Xormal  saline  the  density  of  which  is  practicaliv  the  same  as 
that  of  water  at  i_'o  V.  is  poured  into  the  tul)ing,  the  tap  on 
the  no/zk"  being  closed,  till  the  glass  tube  is  half  full.  .X 
mark  is  made  on  the  tube  at  the  level  of  the  fluid,  or  a  wooden 
clip  is  used  for  the  iiurpose.  The  needle  is  inserted  into  the 
s])ina!  canal.  Whenever  a  drop  of  tluid  ajjpears  the  tap  is 
dosed.  It  is  important  that  only  the  minimum  amount  of 
fluid  should  be  lost,  otherwise  the  reading  will  Ik?  too  low. 
This  is  a  i)oint  to  wliirh  sulTicient  attention  has  not  usually 
been  i)aid.  The  tul)ing  is  now  connected  with  the  needle  and 
both  ta])s  opened.  Minute  oscillations  of  the  fluid  in  the 
glass  lube  i\\\v  to  the  resi>iratory  movements  ought  to  be  seen, 
otherwise  the  readings  are  valueless.  The  glass  tulx?  is  held 
directly  a!)o\e  the  needle  ;it  such  a  height  that  the  fluid  in  it 
returns  to  its  original  level.  The  vertical  height  of  this  level 
above  the  needle  is  measured,  and  the  result  gives  the  cerebro- 
spiti.al  pre-sure  in  niilbineters  of  water. 

The  pressure  \riries  between  ()n  and  150  mm.,  the  average 
being  about  ijo  nun.  A  variety  of  conditions  mav  cause  the 
pressure  to  be  niised.  In  all  forms  of  meningitis  it  is  in- 
creased, unless  the  openings  in  the  roof  of  the  fourth  ventricle 
are  blocked.  Ilie  liighest  readings  are  obtained  in  cerebral 
tumor.      In  a  tumor  of  the  cerebellum   I  have  seen  the  fluid 


I 


li 


PRESSURE   OF   THE   CEREBROSPINAL   FLUID 


35 


spurt  from  one  side  of  the  bed  to  the  other.  It  may  be,  how- 
ever, that  the  high  intracranial  pressure  forces  the  methilhi 
into  tlie  foramen  magnum,  in  whicli  case  the  spinal  pressure 
will  show  no  increase.  Most  of  the  cases  of  general  paralysis 
which  I  have  examined  have  shown  a  pressure  distinctly  alxjve 
the  normal.  Intracranial  ha-morrhage  is  naturally  associated 
with  increased  pressure.  In  children  the  raised  intracranial 
jiresNure  may  be  the  most  important  factor  in  tlie  case,  and  its 
reduction  by  luml)ar  puncture  may  directly  lead  to  the  cure  of 
tlie  conditiiin.  In  condilinns  as>nciated  witli  general  ledenia. 
sucli  as  unenia  and  eclam])sia,  there  may  be  a  high  cerebro- 
spinal pressure,  the  relief  of  wliich  may  lead  to  most  dramatic 
improvement.  The  persistent  headaches  which  form  so 
troublesome  a  complication  in  some  cases  of  ana-mia  can  prob- 
ably be  traced  to  a  (listuri)ance  ^ — -either  a  heightening  or  a 
lowering  —  of  the  intracranial  pressure.  The  undoul)ted  re- 
lationship which  exists  between  the  cerebrospinal  lluid  and  the 
endc^Iympli  of  the  internal  ear  serves  to  explain  how  cases  of 
Meniere's  disease  have  l)een  improved  and  even  cured  by  re- 
I)eated  lumbar  puncture.  I'rom  these  and  other  facts  it  is 
evident  that  the  ])ressure  of  the  cerebrospinal  lluid  is  of  prac- 
tical as  well  as  theoretical  interest,  and  well  worthy  of  further 

study. 

RKV  VMV.SC  ES 

Cassidy,  M.  .\.  ami  l'a;.;c,  C.  M. :  A  metlKid  for  (Icti.Tniini;i,c:  the 
aI)Si)liitc  jiressurc  of  the  cerchrospinal  lluiil.  I'roc.  Rny  Soc.  .Mfcl., 
Loiulon  191 1,  IV,  rt.  I. 


CHAPTER  \II 


I 
■I' 


LIMI5AR   I'LXCTL'RE 

The  ()i)crati()n  of  lunihar  puiuturc  is  now  so  well  known 
aiul  >o  widely  practia'd  lliat  il  i>  umiecessary  to  discuss  it  in 
great  detail.      (  l-ig.  4.  ) 

'i'lie  patient  may  l)e  sittint,^  up  or  lyi.i-  on  one  side.     The 
most  convenient  site  is  tlu    ,paee  l>etween  the  fourth  and  filth 
hinihar  vertebra-,  readily   found  hy  remembering  that  a  line 
joining  the   higlie-t   point>   on  the   iliac  crest   pas>es   through 
the  spine  of  the   fourth  lumhar  vertebra.     The  skin  is  ster- 
ilized with  iodine.      The  hot  needle  is  ,,ne  of  platinum  tipjjed 
\\ilh   iridium.     .\  common   fault  in  lumbar  ])uncture  needles 
IS  to  make  them  too  thick.      This  greatly  adds  to  the  patient's 
di^-comfort.      The    needle    >h.iuld    be    provide.!    with    a    stout 
.-tdette.      A  i)rcliminary  freezing  of  the  skin  with  ethyl  chlor- 
ide   is    often    advi-able.      .\    deep    injection    of    eucain    and 
adrenalin   is  useful   in  nervous  i)atieiits.      More  n-efid,  how- 
ever, than  any  an./stbetic  i>  dsill  on  the  part  of  t!;c  oi)eratoi-. 
I  ho>^e  wlio  have  v.alched  a  tym's  unsuccesst"ul  efforts  to  enter 
tlie  si)inal  canal  will  agree  tli.tt  it  is  advi>al)le.  if  ixissible,  to 
make  the  llr-t  attemi)t>  on  the  cada\er,  or  on  a  patient  under 
a  general   aiuestheiic.     The  clu'ef   thing  to   be  learned   is  the 
difference  betwe-n  the  resistance  of  the  ligamenla  subllava  to 
the  needle,  and   iliat   of  the   vertebne  themselves.      With  the 
hi.lex  fmger  of  the  left  hand  on  the  tip  of  the  spine  of  the 
fourth   lumbar  vertebra,  the  needle  sh,,uld   be  entered  .about 
half  an  inch  to  (me  side  of  and  ;i  little  below  the  spine.      It 
must  be  pushed  forwards,  inwards,  and  a  little  upwards.     The 
upward  mo\ement   i>   imi)ortant  owing  to  the  inclination  of 
the  lamina'.     In  children  it   is  -onu'iime-  !iv>rc  convenient  to 
enter  in  the  middle  of  tlie  line.     A  general  an;esthetic  will 

36 


(« 


III,.    4.       riu'    Imipv   laiiclmarkv    i'..r    IniiiKar    |iuiuliiri' 


I-UMBAR    I'l'NCTLRE 


M 


soinctiiiic's  he  lu-cdnl,  especially  in  cases  of  nieiiinf,ntis  with 
marked  oijisthotoiios.  In  acUiIts  a  general  an;esthetic  slunild 
he  used  in  cases  of  tetanus. 

The  needle  may  enter  the  canal,  and  yet  no  tluid  may  Ix: 
forthconiinjj.  A  stout  stilette  should  Itc  passed  into  the  needle, 
as  a  shred  of  muscle  may  he  Mockinf;  tlie  lumen.  If  this  is 
of  no  avail  it  is  prohahle  that  the  needle  ha-^  not  penetrated 
the  arachnoid,  hut  h:is  merely  pushed  the  memhrane  in  front 
of  it.  In  this  ca-e  another  puncture  should  he  made  in  the 
s|)ace  ahove.  If  the  operator  fails  to  enter  the  canal  it  is 
nuii.'h  hctter  to  withdraw  the  needle  and  try  the  next  space 
than  to  contintK'  hlindly  to  prod  the  unhappy  patient. 

In  rare  c.ise-.  it  may  he  impossihle  to  ohtain  any  lluid  — 
the  so-called  dry  tappiuij^.  F'eforc  assuminj^  that  such  a  con- 
dition exists  it  is  always  well  to  employ  the  two  needle  device. 
In  addition  to  the  needle  already  in  the  canal,  another  is  intro- 
duced into  the  next  s])ace  aho\e.  and  coupled  hy  a  short  len^h 
of  ruhhcr  tuhin-^  to  a  f,dass  cannula.  .\  little  warm  sterile 
saline  is  poured  into  the  cannula,  and  if  the  cimdition  is  reallv 
one  of  dry  tap.  that  is  to  say  if  the  lower  needle  is  really 
lyini^  unhlocked  in  the  s|)inal  canal,  the  saline  will  How  freely 
from  the  latter  needle.  The  onlv  case  of  apparent  ahsence  of 
tlm'd  in  the  lower  part  of  the  spinal  sac  which  I  have  en- 
countered was  (me  of  transverse  myelitis. 

So'ue  of  the  most  difllcult  cases  on  which  to  perform  lumhar 
puncture  are  met  with  in  asylums,  ^•".xeii  in  cases  of  acute 
delirious  mania,  however,  one  can  ahi'ost  always  succeed,  es- 
pecially if  the  patient  Ix?  made  to  sit  astride  of  a  chair  facinc; 
the  hack,  and  with  his  arms  pulled  well  over  the  hack,  which 
should  he  as  low  as  possihie.  In  these  cases  it  is  always  wise 
to  use  a  platimnu  needle,  for  a  steel  one  is  very  liahle  to  hreak 
should  the  patient  suddenly  Iwcjin  to  strucjcjle. 

The  f|uantitv  of  lluid  which  may  he  or  oui^ht  to  he  with- 
drawn <lepeuds  crreatly  on  circuiustanccs.  Tn  the  £jenerality 
of  cnse-;  fnmi  \'i\v  to  ten  cuhic  centimeters  mav  safelv  Ik? 
taken  off.  For  all  ordinnrv  purposes  five  cuhic  centimeters 
are  amply  sufficient,  provided  that  the  various  te.sts  are  carried 


.?8      I'IIVsi()i.(h;v  and  i-atiioiocv  oi-  tmi.  ciriiirosi'inm.  ifiii) 


i 


•  'lit  ill  till-  pri'iHT  onkT.  In  caM'-<  nf  niniiii-iti>  it  is  advisalilc 
to  witlitlrau-  larj^c  amounts  np  to  tliirty,  fi.rt\.  or  fifty  cii^ic 
fcntinirtrrs.  iiuu-h  iK-pcndini:  upon  tlir  r.'tc  of  ,lo\\.  'I'licn-  is 
OIK'  class  of  case,  however,  in  wliicli  too  prcat  care  c.innot  Itc 
c\crci-i'(l.  Most  of  tin-  accidents  and  fatalities  fc.llowin^' 
hiniliar  puncture  —  and  there  is  reason  to  I)elieve  tliat  niaiiv 
such  accidents  .md  fatahties  have  not  k-en  reported  —  ha\  e 
heen  in  cases  of  cerebral  tumor,  and  e>-peciallv  tiunor  of 
tile  posterior  crani.d  fossa.  In  these  case>  the  intracranial 
pressure  is  invariahly  hi,i,'li.  and  if  the  spinal  prc-nre  he  snd- 
deidv  diminished  hy  the  withdrawal  of  fluids,  there  is  ijreat 
d:iii:;i-r  ot  the  niedull.i  heiii'.'  forced  into  the  foramen  mapnim 
with  conseipient  pressure  on  the  vital  centers  which  mav  he 
at!(  tided  l.y  f,it;d  results.  In  a  w.nlar  sarcom.a  with  thin 
v- ailed  \es-.eK  a  sudden  f.all  in  pressure  may  he  folloved  hv  a 
fatal  haiiiorrh.'i'^e.  in  very  much  the  same  u.iv  as  hrm..rrha"-e 
from  the  vessels  in  the  u.all  of  a  loivuf-distcnded  hladder  may 
follow  a  too  liasty  withdrawal  of  urine. 

It  cannot  he  too  stron,L,dy  ur-ed  that  lumhar  i)imcture  is  not 
such  an  essenliallv  harmless  procedure  as  venesection.  A 
fatality  occurrin-:  in  the  cour-e  of  a  pnKcdnre  which  has  proh- 
alily  —  and  nalur.illy  —  Iieen  represented  as  of  a  trivial  nature 

•  Iocs  not  tend  to  cstahlish  the  ]ihysici;ui  in  the  confi  Inire  of 
the  rel.itixcs.  nor  in  rmy  way  to  enhance  his  reputation.  If 
a  tumor  of  the  posterior  cranial  foss,-i  has  l)een  diaLriiosed, 
the  ptmcture  must  only  he  pert'ormed  in  the  recumhent  posture, 
without  a  jiiliow,  .'iid  not  more  than  two  cuhic  centimeters 
-hould  he  w  ithdrawn. 

Schoenheck  has  collected  seventy-one  fatal  ca-^es  from  the 
liter.atnre.  In  fifteen  of  tlie-e  le^s  th;m  five  cuhic  centimeters 
was  withdrawn.  In  -cxen  (Katli  occurred  immediately  after 
the  puncture.  Tn  some  it  w.is  delayed  for  sever.d  hours.  Tn 
ca-es  of  ccrelicnar  tmiior  he  .Khisos  that  the  patient  he  kejit 
in  lte<l  for  _' |  hours  hcfore  and  J-i  Iiours  after  puncture. 

The  i|uestion  of  the  after-effects  of  lumh.ir  puncture  is  one 
v.!;:ch  i.  i;it  ^tifficieiitiv  cmpiiasi/i.-d  hy  many  writers.  Indeed 
in  many  cases  it  is  not  even  referred  to.     .Nmonp^st  those  an- 


I.L  MBAR    PUNCTURE 


30 


t 
III 


tlioritiis  who  do  discuss  the  -iii)jcct  there  is  a  somewhat  re- 
maricalilc  diversity  ot'  opinion.  l'"or  instance  I'haulTanl  and 
I'.oidni  in  a  scries  oi  two  hundred  .uid  tuenty-tlirce  puniiurc- 
rciird  '  nly  I'lree  cases  <'i  voniilinj;  an<l  no  other  ill  citecls 
to  spia.x  ol  uiih  the  exception  oi  >li};ht  iieadache.  N'issl,  nn 
the  o'her  hand,  met  witii  iieadache,  nansea,  vuniiting,  and  in 
.-onie  case-  complete  prostration  in  forly-eii^ht  out  oi  one 
hundred  and  twelve  ca>es  punctured.  Of  seven  doctors 
uhnni  he  punctun.  1  as  control-,  ix  develoi)Cil  severe  synip- 
loni-.  Ill  a  serie-  of  oh>ervation-  of  my  own  upon  one  liun- 
dred  and  iwenlv  asylum  i)atients  I  had  to  record  marked 
after-elTert>  in  l uenty-live  ca>es,  toj;ether  with  sli.Ljhter  sequela- 
in  a  iHimher  more.  'Jlie  chief  symptom-  were  he.idache,  ,i,dddi- 
ness,  naii-e.i,  and  vomiiinj;.  Mo-t  of  the  p.itients  were  kept  in 
hed  for  twenty-four  hours  after  the  puncture,  and  not  more 
than  eij,dit  culiic  centimeters  were  wilhdr.iun.  The  -ymptouis 
as  a  rule  made  their  appearance  si  ion  after  the  patient  Rot  up, 
hut  were  occasionally  delayed  for  an  hour  or  two.  In  one 
rem.irkalile  case  a  weakly  and  an;emic  fjirl  was  kc])t  in  hed 
for  live  day^.  .\t  the  end  of  that  period  she  .L;i)t  up  and  felt 
(|uite  well,  hut  seven  hours  later  she  liad  so  severe  an  .iltack 
of  headache  and  faintncss  tliat  she  hail  to  retire  to  hed. 

'I  o  what  are  we  to  ascrihe  these  divert^ent  and  ai)parently 
contrailictory  results?  I  think  that  the  most  important  factor 
is  the  type  of  case  under  inve>li{jation.  In  a  .general  hospit.al 
if  a  hnnhar  puncture  is  perfonned  on  a  patient  the  pnihahility 
is  that  he  is  distinctly  ill  and  is  unlikely  to  leave  his  hed  for 
manv  davs  after  the  puncture.  I'nder  such  conditions  it  is 
unlikely  that  there  will  he  any  marked  after-effects.  Certainly 
in  hospital  jjatients  I  have  never  seen  after-effects  comprirahle 
in  severity  to  tho.sc  of  asylum  patients.  In  asylum  practice, 
on  the  other  hand,  it  is  prohahle  that  the  i)atient  is  merely 
put  to  hed  for  the  piirpo.se  of  the  puncture,  after  which  he  is 
allowed  to  f^^et  up.  Under  such  conditions  disagreeahle  sym])- 
toms  are  nuich  more  likely  to  follow.  I'ut  even  in  asylum 
v> '  .rk  a  further  di.--tiiKiion  cats  he  made.  The  one  class  of 
case  in  which  I  never  ohscrvcd  any  unpleasant  effects  was  the 


4t>      I■IIVSI()|.(M•,^   AM)  l•.\Tll()l<K;^•  of  tiii;  ckrihrosimnai.  fi.ui-) 

j:ciKTa!  paralytic:  tlu-  oxiikmation  prohaMy  hciiii,'  the  ,;:.,rkc(l 
<.'\cc>.s  (if  iluid  wliiili  i\  ahiin^t  always  i)r(.'-~viit  in  ilii-,  (li^ca-^c. 
il  iidw  a  >cricN  of  (.l)M.Tvatiuiis  |,c  made  on  .iivmral  ])aral\!ics 
the  results  ;;^  re-ariN  after-elUrl--  will  he  ver\  .iirrerenl  from 
those  in  a  series  of  onh'nary  mental  cases.  This,  it  appears  to 
ine.  is  the  nio-t  rea^onahle  expl.ination  of  the  reinarkahle 
iliver-ity  of  the  reports  in  the  literature.  Speaking;-  .i,H'nerally 
It  may  he  said  ilia!  the  niori'  norma!  the  patii'Ut  the  more 
hkel\  i>  he  !m  .;-jTer  fr:.:n  a  I  ter-el'l'ei-t  ;.  \>:!eria-  can's  of 
iiienin.L^eal  irritation  and  of  increa-ed  intracranial  tension  fei'l 
hetter  ratlier  than  wor-e  a-  the  re-nlt  of  tlie  ptuictnre.  Oc- 
ca-ionally  the  headach.e  may  he  p->ychical  in  natun',  for  in  one 
ol  m\  c.i.e-  it  occurred  where  no  thiid  w:;s  oh.tained. 


Rl  ll-Ri:\(|-S 

CtiamT.inl.  A.  mii.!  I'.oidin.  I,.:  Tn  an  dc  poncti.^n.  i.miliairc-  driiis 
ilti   .-ftvicr  lic)-pir,-i!ier.      Cm.  d.  hn]<..    10(14.   F.X.WII.  p.  -j;. 

.Vi<-1:  hie  lUdcntnn;:  ilc<  I .inn!i;iliiiitiktinii  t'tir  die  I'-vclii.itry. 
rcntrallil,   f.    \\t\c.iIi   n.    I '.\clii:it..   !<,<v4.  XWII.  p.  jj;. 

.'^clioeiil.cok.  (>,  :  I  )io  C,...  fall  nil  d.r  I.ii.idialpiinkli.m.  .\rcli.  f. 
kliti.     Cliif.    n;i;.  (AMI.  ji.  ;,o(). 


CHAPTER  VIII 

|•1I^'SK■.\I.  I'ROPKRTIKS 

It  cainint  lie  sail!  that  the  pliysical  ])r(ii)i'rties  of  the  cerebro- 
spinal llnid  are  very  strikiiij,^  or  of  a  specially  positive  char- 
acter. Iiideeil,  althoiij;h  imich  time  and  study  have  been  de- 
voted to  tlieiii  tlie  results  have  not  been  remarkable  either 
from  the  academic  or  the  ])ractical  standpoint.  To  this  state- 
ment, however,  two  exceptions  nmst  be  made.  I'.oth  the  color 
and  the  jjre-^ure  of  the  lluid  are  worthy  of,  and  have  re- 
ceived, careful  con.^ideratioti. 

COLOR 

The  cerebn»pinal  lb  '  '  is  a  perfectly  clear,  limpid,  colorless 
lluid.  which  in  appearai  v  cannot  be  distinj,niislied  from  water. 
The  sli^btest  diverq;ence  from  this  c  ndition  of  limpidity  indi- 
cates a  pathological  condition,  provided  that  certain  possi- 
bilities .-^.re  taken  into  consideration.  l"or,  b.efore  any  con- 
clusions rcij^ardin;.;  morbid  conditions  can  be  drawn,  it  is  first 
essential  to  exclude  the  possibility  that  such  a  (livcr£:;ence  from 
the  normal  luay  have  its  origin  in  the  operation  of  lumbar 
])uucture. 

The  cliief  condition  to  which  an  alteration  in  the  physical 
a])pearauce  of  the  lluid  may  l)e  due  are  the  presence  of  blood 
or  leukocytes. 

The  lluid  which  first  appears  tuay  be  tinged  with  blood. 
This  blood  mav  come  from  one  of  two  sources.  It  may  be 
I)rcexistent  in  the  fluid  owing  to  cerebral  h.vuiorrhage,  frac- 
ture of  the  -kull,  or  injury  to  the  spinal  colunm.  Or  it  may 
come  from  a  ve>sel  which  has  been  ])iuictured  at  the  operation. 
The  tyro  will  frc(|uently  obtain  blood  in  his  earlier  attempts. 
The  expert  who  enters  the  catial  with  one  quick  push  will  be 

4> 


42        1'1IVSI()|.(I(.V    AM)    I'ATIIOI.OCV   or  Tin:  flRCISROSI'IVAI,   FI.UIO 


tniii!>lc<l  in  this  way  imii.-Ii  more  scldnm.  A  fraiiiciit  smiroc 
(i|  iKiiiinrrlKiL;-^  i>  udtiiidiiiir  oi'  tl^.  |)lc-\u>  of  veins  uliicli  lies 
in  the  anteri. .r  wall  ui"  ilie  eaual.  'I'liis  accident  niav  be 
avoided  it  tin-  needle  is  not  intmdnced  too  t'ar  at'ter  tlie  li;^^■l- 
inenta  siilillava  Iiave  lieeii  jtiereed. 

I^veii  witli  the  j;reate-t  cafc.  iiowever.  the  ihiid  uln'ch  lir-t 
i-Mle-^  may  lie  Mood  stained.  The  lir<t  t'ew  dro])s  shonld  lie 
di-carded.  and  the  iv-t  of  the  lluid  collected  in  two  sterile  te^t 
t;;!  es.      '{"he  -ecind  oi'  thee  will  contain  little  or  no  hlood. 

As  a  rule  what  may  he  called  accidental  hlood  may  he  dis- 
tin;;ui>hed  from  ])ree\i<tinj:f  hlood  hv  two  simple  tests.  If 
the  hli.od  i;  accidental  in  or;i.;in  the  i^tream  will  n-nallv  rapiillv 
cle.-ir,  and  there  will  he  a  marked  dift'erence  hetween  the  tnhes. 
Should  a  comparatively  lar-e  vein  have  heen  opened,  Iiowever, 
the  -ecoiiil  tnhe  m;iy  contain  a  \ery  ai)preci,al)le  ifuantity  of 
"oM,!.  In  this  c;ise  the  lluid  mu-t  he  centri fn.i^ed.  If  th.e 
hlocd  i\  (,f  recent  ori:vin,  the  red  corpuscles  will  he  drawn  to 
l':e  1)1  lit. im  and  the  supernatant  (Itiid  hccome  |)erfectlv  clear. 
If,  (ill  the  other  h.and.  it  has  heen  in  the  spinal  canal  for  ;mv 
t:n;e  it  will  have  heconie  h.emoly>ed,  and  centrifuf^iu'^-  will 
ppiduce  little  eft'ect. 

It  nm-t  he  rv.ali/ed,  however,  tha.t  the  jjroccss  of  destruction 
ol  tl'e  red  hh-od  cell-  is  one  which  Lakes  some  little  time,  and 
durii!;^  the  l;r-i  day  or  two  the  cells  m;iy  show  little  altera- 
tion. 

I  he  red  col.inition  due  to  Ireniolv^is  does  not  develop 
fid'v  till  tlie  end  of  the  fir>t  week,  after  which  it  -radually 
hict.nie-  fainter,  till  hy  the  ei'd  of  the  fourth  week  it  m;iy 
ha\c  completely  di>-apiH';ired. 

I  have  .-ein  ;i  ca-e  of  fnacture  of  tlie  skull,  examined  within 
twenly-fMur  h-ur^  of  tlie  injury,  in  which  centrifujjin,!^'  re- 
ti:..ved  cvc'-v  tr:!c.-  of  hi.  m,],  s-nl't'cient  time  t'or  li;emolv-is  to 
he  |)r.  mIu'ciI  U"!  havin;;  e'.ip-ed.  The  -source  of  the  hlood  was 
\'"'>'  evid't;'.  h-'wcver,  u  v  it  w.w  -i >  ahundant  .and  ^o  in- 
timildv  111!- (■  !  Willi  the  lliild  ih.it  it  CMtild  not  po->ihly  Ii;i\c' 
ci  nie  fr'-m  ,i  wi>nnded  vein.  In  some  cases  the  tiiii^in-,'  of 
tlie  superii.it.uti  liuiii  may  he  very  .->li,t;lit.  and  it  mav  oiilv  he 


I'FIYSICAL    PROPERTIES 


43 


detected  wlieii  the  tliiid  is  compared  asji'ainst  a  wliite  back- 
irroiiiid  witli  a  sj)L'ciineii  of  clear  water.  It  is  important  that 
tin's  should  he  reali/.ed.  for  upnn  a  deterniination  of  the  ])res- 
cnce  of  preexistini^  blood  may  depend  the  diafj^nosis  and  the 
(liiestion  of  operation. 

Tint^in:^  of  the  tluid  without  turbidity  is  not  in  every  in- 
stance due  to  cerebral  nr  nieniiiLreal  h;emorrhat,'e.  Of  recent 
years  considerable  attention  has  been  devoted  to  a  peculiar 
yellow  or  f^'olden  tintjint;  of  the  lluid  to  which  the  name  of 
xanthochromia  has  been  applied.  In  this  condition  the  lluid 
is  perfectly  translucent  and  free  from  turbidity,  but  of  a  color 
varyint;^  from  a  pale  straw  to  a  deep  amber.  This  condition 
was  first  described  bv  hVoin  in  U)OX,  and  was  found  by  him 
to  be  associated  with  a  remarkable  increase  in  the  protein  con- 
tent of  the  fluid.  I'ibrin  is  often  jiresent  and  spontaneous 
coa^nlation  of  the  fluid  may  take  place.  Since  that  time  a 
large  number  of  cases  have  been  recorded,  and  it  is  now 
recopiiizcd  that  the  patholoj^Mcal  condition  in  which  this  com- 
bination occurs  most  frequently  is  one  of  pressure  on  the 
spinal  cord  in  which  a  portion  of  the  subarachnoid  sac  is 
shut  off  from  the  rest  of  the  space.  In  this  condition,  al- 
thou,t,di  the  protein  may  be  enormotisly  increased,  there  is  as 
a  rule  no  '-orrespondinsj  increase  in  the  cells  of  the  fluid, 
which  in  many  cases  are  normal  in  number.  This  last  is  the 
most  characteristic  feature  of  all.  It  cannot,  however,  be 
considered  absolutely  pathojijnomom'c.  for  I  have  observed  a 
case,  with  marked  protein  but  no  cellular  increase,  which  at 
ar.topsv  proved  to  be  one  of  tumor  in  the  pituitary  re.s;ion. 

This  phenomenon  will  be  considered  ac^ain  in  a  later  sec- 
tion. At  present  we  are  only  concerned  with  the  presence  of 
colorinpf  matter  in  the  fluid.  It  is  necessary  to  flistintjuish  a 
tnie  xanthochromia  from  colorati<Mi  of  the  fluid  or  erythro- 
chromia  due  to  cerebral  or  menincfcal  h.Tmorrhac^e.  There  arc 
several  rcs|)ects  in  which  the  two  comlitions  differ  from  one 
another. 

In  erythrochromia  marked  chanjjes  in  the  color  of  the  fluid 
may  be  observed  if  a  series  of  punctures  at  intervals  of  a  few 


44        PHYSIOLOGY  AND   PATHOLOGY   OF  TMi;   CIiRKBROSPINAL   FLUID 


(lays  liC  perfortiu'd.  and  liy  tlic  end  nf  tlirce  or  four  weeks  tlic 
color  has  almost  or  entirely  disappeared.  In  xaiithochroniia 
the  color,  which  i-  of  a  more  ,i;-o!den  tini;e,  mav  remain  con- 
stant thron,i,diout  a  ])eriod  of  many  months. 

In  erytiirochromia  well  formed  red  cells  or  the  shadows  of 
.such  cells  can  he  iecoL;ni/'ed  under  the  microscope.  Xo  >nch 
cells  are  present  in  xanthochroini.i. 

In  eryihrochromia  the  chemical,  and  in  the  earl\-  ^-tri'.^es  ll-.c 
si)ectroscopic,  te>ts  for  Mood  |)i;'nient  .ire  |)o>itive.  In  xan- 
thochromia they  ar.-  invariahly  nej:^ative. 

In  er\throchromia  it  i-,  common  to  find  a  m.irked  increase  in 
leukocytes,  owinj,'-  douhtless  to  the  irritation  of  the  meiiiii:,^'- 
produced  hy  the  effused  Mood.  In  xanthochromia,  as  has  al- 
ready heen  mentioned,  it  is  unusu.al  to  find  any  increase  in 
white  cells. 

I'in.illy.  true  xanthochromia  is  comnionlv  met  with  as  a 
late  ])henomenon  in  the  complex  k.own  as  the  Xoime-I'roin 
.syndrome,  of  which  massive  coa,<:^ul;ition  of  the  lluid  is  one 
of  the  most  characteristic  features.  This  never  occur>  in  erv- 
throchromia. 

\\  hen  all  h;i-  heen  said,  however,  there  remain  cases  in  which 
the  coloration  of  the  thiid  is  ditTicult  to  cl.issifv.  In  one  case 
which  I  reported  a  m.arked  yellow  coloration  suddenly  ap- 
pe'>-ed  in  the  fluid  of  a  case  of  acute  mem'n^itis  which  was  he- 
inc:  treated  hy  repeated  lumh.ir  jiuncture.  The  ihiid  showed 
no  traces  of  Mood  cells,  hm  the  color  onlv  persisted  for  a 
few  weeks.  There  was  no  coincident  increase  in  the  pro- 
tein. 

The  source  of  the  colorinsj:  m.atter  in  xanthochromia  must 
almost  certainly  he  the  hlood.  hut  wh.at  the  exact  mechanism 
may  he,  whether  hy  minute  ha-morrhaj^'es  into  the  statjnant  cul- 
de-sac  or  hy  some  other  means,  is  at  present  onlv  a  m.itter  for 
conjecture,  'i'he  prevalent  view  is  that  the  color  is  due  to 
capillary  h;emorrhaj:es,  with  ver^-  slow  disintesjration  of  the  red 
cells,  with  a  result  snnieuhat  .analoi^'ous  to  the  coloration  met 
with  in  ha'molytic  jaundice.  Mestrczat  states  tliat  hy  n>int^ 
refined  methods  he  was  able  to  <l<,-mon.strate  the  presence  of 


PHYSICAL    PROPERTIES 


45 


ur()l)iliii  in  sucli  tluids.     Certainly  this  cannot  be  done  by  using 
tlie  ordinary  tc^^t.s  for  bile. 

Jaundice.  Tlic  tlnid  may  \k  bile  stained.  It  is  sometimes 
stated  that  the  cerebrospinal  tluid  escapes  the  universal  ting- 
iiii;  wliicli  i>  found  in  biliary  jaundice.  This,  however,  is  only 
nirtial  truth.  Whilst  it  is  the  case  that  the  spinal  fluid 
IS  less  colored  than  any  other  of  the  body  fluids,  yet  in  many 
cases  a  careful  examination  will  reveal  a  distinct  yellowish 
tiu'^e.  Tile  healthy  choroid  ple.xus  presents  an  impenetrable 
barrier  to  the  passaj;e  of  the  constituents  of  the  bile,  and  es- 
pecially of  the  bile  salts,  into  the  spinal  fluid.  In  severe 
cases,  however,  the  epithelium  covering  the  plexuses  may  be- 
come so  damaj^ed  that  they  allow  the  passage  of  at  least  the 
pigments  of  the  bile  into  the  spinal  fluid.  In  no  instance, 
however,  does  the  coloration  met  with  approach  to  that  met 
with  in  the  other  body  tluids.  In  one  case  of  ha?molytic 
jaundice,  in  wliicli  the  blood  serum  was  highly  charged  with 
bile  i>igmei..-.  Init  the  urine  coni])lelel\  free,  I  examined  the 
-spinal  lluid  with  great  care  for  bile  pigmeiUs,  but  was  unable 
to  detect  the  slightest  trace. 

Turbidity  of  the  tluid  indicates  the  presence  of  an  abnormal 
number  of  cells.     These  cells  may  be: 

1.  Red  blood  corpuscles,  derived  from  a  cerebral  or  menin- 
geal ha-morrhage.  or  from  a  vessel  wounded  by  the  puncture. 

2.  rolymor|)honuclear  leukocytes,  which  are  present  in 
enormous  numbers  in  acute  meningeal  infections. 

3.  Lymphocytes.  .\s  a  rule  the  presence  of  lymphocytes 
lends  no  turbidity  to  the  fluid,  and  they  may  be  present  in  con- 
siderable numbers  without  afifecting  its  limpidity.  When, 
however,  the  numbers  are  very  high  they  may  impart  a  dis- 
tinct turbidity,  or  rather  opalescence,  to  the  fluid.  In  one  of 
m\'  cases  of  early  general  paralysis  of  the  insane  in  which  a 
very  large  cellular  increase  was  present  the  appearance  of  the 
fluid  was  distinctiv  turbid. 

Pressure.     This  has  been  fully  di.scu^sed  in  Chapter  VI. 
Freezing  point.     The  freezing  point  of  a  fluid  is  dependent 
on  the  quantity  of  dissolved  substances  which  it  contains,  and 


46       PllVSIOI.OGV  AND   PATHOI.OOY  OF  TIIH  CFREBROSPINAL  FLUID 


thus  aft'Dnls  an  indication  of  tlic  molecular  concentration  of 
tiie  lluid.  At  one  time  it  was  lioped  tliat  valuable  information 
might  be  provided  by  the  determination  of  the  freezing  point 
of  the  cerebrosjiinal  fluid,  and  numerous  cryoscopic  observa- 
tions have  been  made  with  that  end  in  view.  It  cannot  be 
said,  however,  that  these  investigations  have  revealed  much 
of  importance.  The  normal  freezing  point  is  given  by  Mes- 
trexat  as  -0.575.  '""  ''mything  from  -0.51  to  -o.5>^  C.  may  be 
ct)nsidered  as  being  within  the  normal  limits. 

The  ch'clriciil  condnctiiity  is  another  property  of  minor  im- 
portance which  has  received  some  attenti(>n.  It  is  sufficient  to 
say  that  the  fewer  are  the  dissolved  substances  in  the  fluid, 
the  poorer  is  its  power  of  conduction. 

'Ihe  sf'ccific  <jriU'ity  varies  little,  being  usually  between  1006 
and  icx^*^. 

Reaction.  The  cerebrospinal  lluid  is  faintly  alkaline  in 
reaction,  owing  to  the  salts  which  are  dissolved  in  it.  Cavaz- 
zani  in  iSi)j  asserted  that  the  alkalinity  was  half  that  of  the 
blood,  a  statement  which  has  l)een  faithfully  transcribed  by 
most  succeeding  writers.  Of  late  much  attention  has  been 
devoted  to  the  alkalinity  of  the  blood,  and  methods  for  its 
deterniitiation  iiave  I)cen  considerably  simplified.  The  most 
convenient  means  of  expressing  the  alkalinity  of  such  a  fluid 
as  the  blood  is  in  terms  of  the  iiydrogen-ion  concentration, 
which  may  very  readily  be  determined  by  the  method  of  Levy, 
Rowntree,  and  .Marriott.  This  method  is  so  eminently  .suited 
for  such  v.'ork  on  the  cerebrospinal  fluid  that  it  has  already 
licen  applied  to  that  purpose  by  several  workers. 

Tile  main  difficulty  that  stands  in  the  way  of  the  colori- 
metric  method  for  determining  the  hydrogen-ion  content  of 
the  blood  serum  is  the  presence  of  coloring  matter  and  protein. 
The  first  of  these  is  not  found  in  the  cerebrospinal  fluid.  As 
for  the  second  the  annjunt  of  protein  normally  present  is  so 
small  that  it  may  be  disregarded.  If.  however,  a  large 
amount  of  albumin  is  present  it  can  l>e  readily  removed  by 
dialysing  the  fluid  through  :i  roHodioP.  sac,  one  cu.bic  centimeter 
being  (ii.ilysed  .'ig.iinst  three  cubic  centimeters  of  o.S  per  cent. 


PHYSICAL    PROPERTIES 


47 


solution  of  pure  sodium  chloride.  The  preparation  of  these 
sacs  by  the  method  usually  recommended  is  one  of  consider- 
able difficulty.  Collodion  is  poured  in  and  out  of  a  small 
test-tulx;,  the  film  which  forms  on  the  surface  is  allowe<l  to 
dry,  and  is  finally  separated  from  the  glass  with  the  point 
of  a  knife.  Unfortunately  there  is  a  great  tendency  for  the 
bottom  of  the  collodion  sac  to  adhere  to  the  glass,  with  the 
result  that  a  tear  occurs  when  the  sac  is  withdrawn,  and  the 
sac  thus  rendered  useless.  I  have  found  that  a  simple  device 
will  overcome  this  difficidty.  and  render  the  preparation  of  the 
.sacs  a  matter  of  case.  Melted  gelatin  is  poured  in  and  out 
of  the  test-tube,  and  the  film  allowed  to  dry.  Collodion  is 
then  poured  in  and  out  of  the  tube  and  also  allowed  to  dry. 
The  tube  is  filled  with  cold  water  to  harden  the  collodion  coat, 
and  then  placed  in  the  incubator.  The  gelatin  melts  and  the 
collodion  sac  can  be  removed  intact  from  the  test-tube. 

If  there  is  no  excess  of  protein  and  no  blood  is  present  it 
is  unnecessary  to  dialyse  the  fluid,  for  practically  identical 
results  arc  obtained  with  dialysed  and  undialysed  specimens. 
To  3  c.c.  of  cerebrospinal  fluid  in  a  small  test-tube  lo  by  loo 
mm.  is  added  0.3  c.c  of  a  o.oi  per  cent,  solution  of  phenolsul- 
phoiic]>hthalcin.  The  color  produced  is  compared  with  a 
standard  set  of  tubes  containins;  varying  proportions  of  acid 
potassium  phosphate,  Klf^.PO  ,  and  .alkaline  sodium  phos- 
phate, Na^.HPO,.  Such  a  set  of  tulies  may  be  obtained  from 
Hviison,  Westcott,  and  Dunning,  of  Raltimorc,  or  the  solutions 
may  be  prepared  in  the  manner  described  by  Levy,  Rowntree, 
and  Marriott  in  their  original  paper. 

The  first  extensive  series  of  observations  was  that  of  Hur- 
witz  and  Tranter  who  fotuid  that  the  average  hydrogen-ion 
concentration  of  the  fluid  was  8.TI,  as  compared  with  7.6  to 
7.S  for  the  average  of  the  blood.  Weston  obtained  similar 
results  by  the  same  method.  Felton,  ITusscy,  and  Basque- 
Tones,  however,  have  pointed  out  one  important  source  of 
error.  They  insist  that  the  estimation  must  be  made  im- 
mediately after  the-  withdrawal  of  the  fluid,  otherwise  the 
rapid  escape  of  the  carbon  dioxide  in  the  fluid  will  materially 


48       PHYSIOUXIY  AND   I'ATHOLOC.Y  OF  THE  CERUBRDSIMNAI.   FLUID 

increase  the  alkalinity.  They  olxservcd  the  efYect  of  exposing 
the  tUiid  to  tlic  air,  and  fomid  that  in  many  cases  an  exposure 
of  >ix  hours  would  change  the  pH  from  •;.■;  to  S/).  I'sing 
the  method  of  immediate  examination  they  concluded  that  the 
average  pH  t)f  the  cerebrospinal  Ihiid  e(|uals  7.73,  and  that  the 
hvdrogen-ion  concentration  of  the  hlood  serum  and  spinal 
tluid  are  approximately  e<|ual.  They  examined  the  tluid  from 
a  large  mnn!)Lr  of  ca^es  of  nervous  disease,  including  epilepsy 
and  svphilis  of  tiie  ncrvnus  system,  hut  found  no  apprecialile 
alterations  in  the  reaction. 

Levinson  has  described  another  simple  method  of  estimat- 
ing the  alkalinity  of  the  thiiil.  He  titrates  the  ihiid  against 
n/ioo  sulphuric  acid,  using  methyl  red  as  an  indicator.  To 
one  c.c.  of  spinal  fluid,  diluted  with  jo  c.c.  of  distilled  water 
is  added  i  drop  of  a  2  per  cent,  solution  of  methyl  red.  and 
the  numl)er  of  c.  c.  of  n  100  H^.SO^  refjuired  to  produce  color 
changes  is  taken  as  the  index.  The  normal  fluid  gives 
an  index  varying  between  -'.o  and  J. 5  c.c.  The  alkalinity  as 
tested  l)v  this  method  is  considerably  lowered  in  epidemic  men- 
ingitis, ranging  l)Ctween  0.7  and  1.3  c.c,  but  in  tuberculous 
meningitis  there  appears  to  be  little  change. 


REFEREXCES 

Cavazzaiii :  ("ontrihntioii'i  a  la  I'liysioldtjic  (hi  li(|iii(lc  ccrchro- 
spinale.     Arch.  Ital.  de  Riol.  XXXVII.  p.  ,^0. 

Eflton,  1..  D..  Hii^^-ey.  R.  <'■..  ami  P.a^iim-Jono'-,  S. :  Tlic  reaction 
of  the  cerehrnspinal  fluid.  Preliminary  report  on  hydrof;en-ion  con- 
centration as  determined  hy  the  colorinntric  method.  Arch.  Ii't. 
Med..  1917.  XIX,  !n.«!5. 

Ilancs.  E.  M.:  The  spinal  fluid  >\ndr()mes  of  Xouue  and  I'roin 
and  their  diafinostic  si.i:;nificance.  .\ni.  Jour.  Med.  Sc..  ii)if).  ("I.H. 
p.  66. 

Ilurwitz.  S.  II.  and  Tranter,  C  I..:  On  the  reaction  of  the  cerebro- 
spinal fluid.     .\rch.  Int.  Med.,  iQi^'.  X\'II,  p.  S.'S. 

Levinson.     A.:     Studies     in     spinal     fluid.     Arch.     Pediat.,     K)if>, 

xxxin,  p.  241. 

Lev\,  R.  T...  Rowntrec,  I-.  ^'.,  and  Marriott,  W.  Mck. :  .\  simple 
method  for  determininp;  variations  in  tlie  liydrotjcn-ion  concentration 
of  the  hlood.    Arch,  Int.  Med..  191 5.  XVI.  p.  389. 


CHAPTER  IX  ^«) 

cm- MICA L  COMPOSITION 

The  cercl)n)s|)inal  tluiil  is  in  many  ways  a  unique  fluid. 
Although  taking;  its  orij^Mii  directly  from  the  blood  it  differs 
diametrically  from  the  seium  in  the  remarkable  simplicity  of 
its  chemical  composition.  That  composition  may  Ix;  described 
in  a  \V(jrd  by  sayinjf  that  the  fluid  differs  from  distilled  water 
in  that  it  contains  traces  of  a  few  salts,  a  trace  of  protein,  a 
trace  of  snjjar.  a  trace  of  urea,  and  is  alkaline  in  reaction. 
There  is  a  certain  dani,a'r  of  !)eing  led  by  this  simplicity  of 
composition  to  nei;iect  the  chemical  conditions  in  favor  of 
the  more  obvious  cytoloj^ical  changes  which  are  met  with  in 
disease  of  the  nervous  system.  In  such  disease,  however, 
chanties  of  the  jjreatest  importance  may  take  place  in  the 
chemical  composition  of  the  thiid.  and  in  this  direction  lies 
perhaps  the  greatest  hope  that  eventually  fuller  light  will  be 
shed  upon  the  nature  of  nervous  diseases  which  are  at  present 
entirely  obscure.  One  oI)stacle  in  the  way  of  progress  is  the 
coarseness  of  some  of  the  methods  commonly  employed.  It 
is  nnly  when  >uc]i  tests  as  the  W'assermann  and  the  colloidal 
ijold  are  a])i)lie(i  to  the  tluid  that  we  l)egin  to  realize  the  jxis- 
sibilities  of  chemical  investigations  on  the  fluid.  It  is  incon- 
ceivable that  the  fluid  which  bathes  the  nervous  tissues  and 
which  receives  the  products  of  their  metabolism  should  be 
perfectly  normal  in  such  an  essentially  toxic  condition  as  dis- 
seminated sclerosis,  and  yet  because  we  can  demonstrate  no 
increase  of  cells  or  of  |)rotein  content  we  are  forced  to  call 
it  so.  There  can  be  no  doubt  that  as  our  methods  of  investi- 
gation become  more  and  more  refined  and  penetrating,  chem- 
ical auii  biol(i;;!eal  changes  will  be  revealed  in  the  fluid  which 
were  never  dreamt  of  in  our  philosophy. 

49 


u 


5'> 


I'lIVSKlI.OCY  AM)    I'ATIIOI.OCY  OF  TIIF.  CI.REBROSIMNAL  FLUID 


PROTEIN 

IMiMul  scrum  coiitaiiis  a  large  amount  of  albuminous  ma- 
terial, of  which  the  chief  constituents  are  serum  albumen  and 
surum  globulin,   which  are  i)resent  in  the  i)roi)orlion  of  J.3 
per  cent,  of  serum  albumen  and  40  per  cent,  of  serum  globuhn. 
l-or  puri)o>es  of  nomenclature  it  is  C(.nvenient  when  ilealmg 
with  the  cerebrospinal   Ihiid  to  include  these  two  substances 
under  the  common  term  i)rotein.     Sermn  globulin  nny  be  pre- 
cii)ilatcd  bv  half  saturating  the  lluid  with  anunouium  sulphate 
(i.e.  by  adding  an  e-iual  (luantity  of  anim.juium  sulphate  solu- 
tion).'or  bv  fully  saturating  it  with  magnesium  .sulphate.     If 
serum  albumen  is  present  it  may  be  demonstrated  in  the  filtered 
tluid  l>v  heating.     It  is  removed  by  completely  saturating  the 
lluid  with  anunonium  sulphate. 

investigations  on  the  protein  content  of  the  cerebrospinal 
lluid  have  been  conducted  over  a  considerable  lumiber  of  years. 
and  m.inv  and  varicl  have  been  the  results.  It  has  U-en  stated 
at  differJnt  times  that  the  lluid  contains  albumen,  globulin,  al- 
bumose,  nucleo-protein,  and  various  combinations  of  these 
substances. 

It  is  now  universally  admitted  that  the  most  important 
constituent  is  globulin,  which  may  readily  be  detected.  Many 
authorities  state  that  the  normal  iluid  never  contains  true  al- 
bumen, but  undoubtedly  in  some  cases  when  the  globulin  has 
been  completely  removed  minute  traces  of  albumen  can  be 
demonstrated.  The  (luantity,  however,  is  so  small  that  for 
practical  purposes  it  may  be  neglected.  Mestrczat  in  one  case 
estimated  the  amomU  of  albumen  as  being  .004  per  cent. 

Cdolnilin  i.  present  normally  to  the  extent  of  .02  to  .03  per 
cent.  It  reacts  readily  to  such  tests  as  heat  or  the  nitric  acid 
ring  test.  In  many  pathological  conditions  it  is  increased  in 
amotmt.  and  the  detection  of  this  increase  is  of  the  greatest 
importance.  It  is  necessary,  therefore,  to  etnploy  a  test  which 
will  give  a  positive  result  when  the  globulin  is  increased  be- 
yond the  normal  limits,  but  which  will  not  react  with  the 
normal  lluid. 


CHEMICAF.   COMPOSITION 


5> 


From  lime  to  time  a  multitude  of  tests  have  been  devised 
and  suj,'^ested  for  this  purpose.  Of  tli  ^c  three  may  be  highly 
recommended.  Xotliiii};  is  to  be  f,'ainerl  by  de^.ribinj;  the 
others  in  detail.  Before  applying  any  of  the  t.  is  the  fluid 
shoiild  if  necessary  l)c  thoroughly  centrifuged,  so  that  any 
blood  or  pus  cells  may  l>e  removed. 

The  ammonium  .sulphate  ring  test  of  Ross  and  Jones  has 
no  equal  for  demonstrating  the  slightest  increase  in  the  pro- 
tein of  the  fluid,  but  I  have  found  that  e\en  in  normal  fluids, 
if  the  observations  be  made  unuer  th  most  favorable  condi- 
tions, a  positive  result  may  sometimes  lie  obtained. 

The  test  is  made  as  follows.  A  saturated  solution  of  pure 
neutral  ammonium  sulphate  ■  prepared  with  the  aid  of  heat. 
Unless  care  be  taken  to  insure  that  the  solution  is  completely 
saturated  the  results  will  not  l)c  trustworthy.  On  to  the 
surface  of  this  .saturated  solution  is  poured  1  c.c.  of  cerebro- 
.spinal  fluid,  in  the  >ame  manner  ;is  in  the  nitric  acid  test  for 
albumen  in  the  urine.  .\  positive  reaction  is  indicated  by 
the  appearance  at  the  line  of  junction  of  the  fluids  of  an 
extremely  thin,  clear-cut,  white  line,  no  thicker  than  a  sheet 
of  fine  paper,  and  of  a  colnvebby  appearance.  An  indistinct 
haze  nuist  always  be  regarded  as  indicating  a  negative  reaction. 
In  order  that  the  faintest  ring  may  be  detected  it  is  necessary 
that  a  suitable  illumination  and  background  be  used.  It  is 
best  to  use  an  artificial  light  coming  from  the  side  and  a 
black  background.  .\  black  lined  bo.x  in  one  side  of  which 
there  is  an  opening  for  an  electric  light  is  an  ideal  arrange- 
ment. If  a  negative  result  be  obtained  with  this  test,  em- 
ploying the  above  precautions,  there  is  no  excess  of  protein 
present. 

The  original  and  classic  form  of  the  ammonium  sulphate 
test  is  the  Phase  I  test  of  Xonne  and  Apelt,  which  consists  in 
the  addition  of  an  equal  (|uantity  of  saturated  ammonium 
sulphate  solution  to  the  cerebrospinal  fluid.  If  turbidity  ap- 
pears within  three  minutes  the  test  is  positive.  Phase  II  con- 
sists in  the  demonstration  of  the  presence  of  albumen  after  all 
the  globulin  has  been  precipitated  by  ammonium  sulphate. 


52       PIIVSIOUKIY  ANU   PATIIOUK.Y  OF  Tllli  CERLBROSIMSAI.   FLUID 

Nu};iKlii'.>  l)Ut>ric  .iciil  WA  coii^isl^  in  lUf  ;ulilitii>ti  of  0.5 
c.c.  1)1  10  per  cent.  l)Utyric  acid  in  iioniial  saline  tn  0.1  c.c. 
ui  ccrchni-pinal  lluid.  I  lie  tUiid  i^  licalcd.  0.1  c.c.  of  a  4  per 
cent,  .solution  oi  .Midiuni  livilrate  is  ailded,  and  heat  is  again 
applied.  It"  tlie  protein  i>  increased  tliere  uill  appear  in  a 
lew  minutes  tine  tlocculi.  wiiicli  gradually  U'conie  eoarser,  aiul 
finally  form  a  precipitate  on  the  bottom  oi'  the  lu'"'.  1  he 
test  is  a  somewhat  malodorous  one. 

Ihe  third  and  simplest  of  these  tests  is  that  of  Tandy, 
ihe  reagent  is  a  to  per  cent,  solution  of  carlK)lic  acid,  which 
nnist  ])e  prepared  with  care.  The  solution,  which  is  made  up 
with  distilled  water,  is  well  shaken  and  placed  in  the  incubator 
for  some  hours.  It  is  allowed  to  stand  at  room  temperature 
for  several  days,  and  the  clear  supernatant  fluid  is  then  pipetted 
off.  The  test  is  i)erformed  by  allowing  a  drop  of  cerebro- 
spinal lluid  to  fall  upon  the  surface  of  the  reagent.  It  is 
Usually  recommended  that  the  lluid  should  be  allowed  to 
trickle  down  the  side  of  a  watch  glass  containing  the  reagent, 
i)Ut  a  test  tul»e  viewed  against  a  black  background  shows  the 
reaction  perfectly.  .\  positive  reaction  is  indicated  by  cloudi- 
ness or  wliite  precipitate  as  the  drop  of  lluid  i)asses  through 
the  reagent. 

It  will  be  .seen  that  all  these  tests  are  essentially  simple,  as 
simple  indeed  as  the  corresponding  tests  for  albumcm  in  the 
urine.  .\'o  complicated  ai)paratus  is  needed,  and  they  can  be 
performed  in  the  consulting  room  or  by  the  I)edside.  To 
determine  whether  the  cerebros])inaI  fluid  contains  an  increased 
amount  of  albumen  is  as  important,  and  in  some  cases  much 
more  imiiortant.  than  to  decide  a  similar  (|uestion  with  regard 
to  the  urine.  If  this  fact  were  more  generally  recognized, 
what  mav  be  called  l)edside  tests  for  the  spinal  lluid  would  un- 
doubtedlv  become  nuich  connnoner.  The  demonstration  of 
albumen  in  the  spinal  lUiid  may  settle  a  diagnosis  id'  tuber- 
culous meningitis,  general  paralysis  of  the  insane,  or  tumor 
of  the  spinal  cord.  Although  it  may  be  possible  to  do  as 
little  for  these  conditions  as  for  chronic  r>righl"s  disease,  the 
question  of  prognosis  is  even  more  important. 


CHEMICAI-   COMPOSITION 


53 


riic  protfiii  content  of  the  cereI)rospinal  tliiid  will  k-  con- 
sidered when  the  difTereiit  diseases  of  the  central  nervous 
system  are  >tndied.  hut  it  may  Ik.-  well  here  to  mention  the  con- 
ditions in  uhich  it  may  lie  increased. 

A  very  jjreat  increase  is  present  in  acute  meninjjitis, 
whetiier  due  to  the  meningococcus,  the  pneumococcus,  or  the 
streptococcus.  In  tulwrculous  meningitis  there  is  a  marked 
increase,  alllioui^rh  the  thiid  may  appear  perfectly  normal  to 
the  naked  eye.  In  syphilitic  disease  of  the  nervous  system, 
in  j^cnera!  paralysis,  and  in  talies  dorsaiis  it  is  increased  in 
the  K'reat  majority  of  cases.  Cases  of  hrain  tumor  may 
show  an  increase,  hut  as  a  rule  they  do  not;  no  general  rule 
can  he  stated.  The  condition  in  which  the  greatest  increase 
may  occur  is  pressure  on  the  spinal  cord,  usually  due  to  tumor 
of  the  cord.  In  a  numk-r  of  different  types  of  insanity,  in 
which  there  was  no  evidence  of  syphilitic  involvement  of  the 
nervous  system,  I  have  found  a  slight  protein  increa.se.  The 
chief  of  these  were  manic-depre.ssive  in.sanity,  epilep.sy,  de- 
mentia pracox,  and  congenital  imhecility.  These  were  only 
exceptional  cases,  however,  and  the  increase  was  usually  very 
slight. 

The  fact  that  alhumen  is  present  in  pathological  amount  in 
a  variety  of  conditions  does  not  detract  from  the  diagnostic 
value  of  the  sign.  The  diagnosis  may  lie  k-tween  meningitis 
and  meningism.  or  tahes  dorsaiis  and  peripheral  neuritis,  or 
general  paralysis  and  alcoholic  insanity.  In  all  of  these  in- 
stances the  presence  of  alhimien  would  at  once  .settle  the 
diagnosis.  On  the  other  hand  the  test  would  he  of  no  value 
in  distinguishing  hetween  disseminated  sclerosis  and  hysteria, 
or  hetween  general  paralysis  and  cerehrosuinal  syphilis. 

THE  POTASSIUM  PERMANGANATE  INDEX 

It  is  a  well  known  fact  that  water  containing  organic  mat- 
ter has  the  power  of  reducing  a  .solution  of  potassium  perman- 
ganate. This  property  has  ken  utilized  for  the  detection  of 
organic  matter  of  mHammatory  origin  in  the  cerehrospinal 
fluid.     What  ir.  called  the  reduction  index  is  the  numkr  of 


54       PHYSIOLOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

cubic  cciitinictcrs  of  (IcciiKirinal  i)iUa>siiini  pcrinanf^anate  solu- 
tion which  wlien  l)oilc(l  fur  ten  minutes  in  a  strongly  acid 
tiKilinin  are  rethiccd  )iv  i  c.c.  of  cereliros;-inal  .Inid. 

The  te>«t  i>  performed  as  follows.  To  i  c.c.  of  cerehro- 
spinal  thiid  are  added  50  c.c.  of  water,  ici  c.c.  of  1  in  4  sul- 
jdniric  acitl  and  10  c.c.  of  decinorinal  potassium  permanganate, 
and  the  mixture  Iioiled  for  ten  minutes.  To  the  mixture  are 
added  10  c.c.  of  decinorinal  oxalic  acid,  and  the  whole  is 
titrated  with  potassium  permanganate  till  the  characteristic 
color  returns.  I'elow  _■  is  a  normal  index:  from  2  to  2.5 
may  Ix?  regarded  as  iMirderdine  cases,  and  ahove  J. 5  as  high. 
The  higher  the  content  of  organic  substances  in  the  fluid, 
the  greater  will  lie  the  anioutU  of  potassium  permanganate 
solution  reduced. 

The  ci-e-;  in  wliicli  the  te^t  is  most  useful  are  those  with  a 
clear  l1uid  au'l  -yiunt' ivi-  '.u'-.'ge^tive  of  meiu'iigitis.  such  con- 
dition-, for  in-l;nice,  a-  tn'im'ulous  meningitis  or  anterior 
polioinyeliti-.  'Ilure  i-  uo  (k''"nite  relation  between  the  re- 
duction index  and  the  cell  count.  Hoffman  and  Schwartz 
record  a  case  of  cerebral  tumor  which  closely  simulated  tuber- 
culous meningitis;  the  lluid  \' as  opaloceni,  contained  3,^0 
cells  per  c.inm.,  the  majtirity  of  which  were  lymphocytes.  The 
reduction  index,  however,  never  witit  above  the  nonnal. 
There  is  a  much  closer  relati<in  between  the  index  and  the 
globulin,  but  the  former  h;\s  tlu'  ;idvanl.'ige  of  being  more 
readily  expressed  in  figures. 

-Ml  normal  and  noii-inllnnniatory  fluids  give  a  normal  read- 
ing. Borderline  results  are  found  in  the  early  stages  of  in- 
flanunation  of  tlu'  br.ain  and  the  lurninges,  .and  in  st-rous  men- 
ingitis. .\  luLih  index  sinr),-fie-  acute  innanimation  of  the 
brain  or  meninges.  The  test  is  especially  valu:d>le  in  pro;,'- 
nosis.  In  nieningococcus  meningitis  if  the  prognosis  is  good 
the  index  f,ill>  after  the  injiTtion  of  scrum,  even  althouf^h  the 
serum  it-^elf  has  a  high  redi'ction  v.dne.  An  index  remain- 
ing ]ier-istentl\  hii;li.  "n  the  other  li;uid,  i^  ;i  \('r\'  unf;;vor- 
able  siirn. 


CHEMICAL   COMPOSITION 


55 


SUGAR 

'I'lic  ccrchrospinal  li  :ontaiiis  dextrose.  That  fact  is  un- 
(Unil)tc(l,  and  yet  it  is  cmarkalile  how  timidly  many  writers 
approacii  the  suhjcct.  Tiicy  appear  to  he  afraid  to  make  so 
starlhiig  an  adniis.^on.  The  utmost  length  they  are  pre- 
pared to  j;o  is  to  admit  that  a  l'"ehlin<;[-reducing  substance  is 
present  in  the  lluid.  The  explanation  of  this  unwillingness 
1(1  admit  the  presence  of  .sugar  in  the  fluid  is  probably  trace- 
able in  many  instance.-,  to  Halliburton's  statement  to  the  effect 
ihat  the  hehling-reducing  substance  was  not  dextrose  but 
pvrocatechin,  a  pronouncement  which  appears  to  have  been 
received  with  a  remarkable  degree  of  docility.  Halliburton 
himself,  however,  has  for  some  time  revoked  hi.s  opinion, 
and  the  pyrucalcchin  itlea  may  well  receive  a  decent  burial. 
The  sugar  reduces  I'"ehling's  .soluti(jn,  is  fermentable,  rotates 
polari/cd  light  to  the  right,  and  when  treated  with  phenylhy- 
(Irazin  gives  crystals  of  glucosazone  melting  at  202-205''  C. 

The  iiiirmal  cerel)r()spinal  lluid  reduces  Tehling's  solution  to 
a  slight  but  di.stinct  extent.  There  may  not  be  much  color 
change  in  the  sulution,  but  if  the  tulx;  be  allowed  to  stand 
for  a  few  minutes  a  reddish  deposit  will  be  found  at  the  bot- 
ti)in.  An  excess  nl  I'ehling's  solution  should  be  avoided,  and 
it  is  v>ell  to  dilute  the  .solution  three  or  four  times.  Any  ex- 
cess of  albumen  present  should  lirst  be  removed  by  Ixjiling,  as 
it  is  apt  to  give  a  greenish  j)recipitatc  which  may  lie  mislead- 
ing. The  amount  of  sugar  present  is  so  small  that  for  its 
(|uantitative  estimation  sincial  methods  are  necessary.  The 
most  convenient  is  that  of  Myer-  and  luiiley  for  determining 
the  sugar  in  the  iil.iod.  To  _•  c.c.  of  i-erebrospinal  lluid  are 
added  0.2  gm.  of  dry  picric  acid  and  1  c.c.  of  a  20  per  cent, 
solution  ol  sodium  carbonate.  The  tube  is  placed  in  the  water 
bath  at  100  C".  for  20  minutes,  and  the  canary  yellow  color 
produced  is  compared  with  a  standard  solution  of  picric 
aciil  in  an  .Xutenrieth-Kcinig.sbergcr  wedge  colorimeter. 

Weston,    in   a   series   of   observations   on    insane   patients, 
found  that  the  general  average  was  0.068  per  cent.,  that  of 


56       PHYSIOLOGY  AM)   PATFIOLOCY  OF  THE  CEREBROSPINAL  FLUID 

lilooi!  hfiiij;  n.114  IHT  cent.  There  were  eoiisiderahle  indi- 
\iiliial  ilitVereiice-,  1  ut  the  a\eni,t;e  of  the  (liftVreiit  t^'roiips  was 
very  constant.  These  were  as  follows:  inanic-(le])re.>si\e  in- 
sanity 0.0711.  t'i''''-'P^y  0.0740.  iinhecility  o.o7j^^,  -.general 
|)aresis  o.od^S,  (k-nieiitia  pnecox  o.<)fM)4. 

I'he  statement  is  ijenerally  made  that  in  acute  suppurative 
menin.ijitis  the  sn<,\ir  is  markedly  decreased  or  altoj^ether  ab- 
sent. In  tulterculous  ineninjjitis  tlie  <liminution  may  I)c  sh^ht. 
These  statements.  Iiowever.  lacked  the  sound  foundation  of  a 
quantitative  estimation  expressed  in  fif^ures.  and  as  a  rule  one 
had  to  he  satisfied  with  the  assurance  that  the  thiid  did  not 
reduce  l\'hlin,i,'"s  solution  well.  I'circe.  working  in  the  lalK)ra- 
tory  of  the  W'iimipej,  (a-neral  Hospital,  and  usinjj  a  technic 
similar  to  that  ju-^t  der-crilicd.  althou<;li  somcwiiat  modified,  ob- 
tained fij,nires  which  bore  out  the  contention  that  in  acute  sup- 
purative conditions  of  the  lueninjjes  there  is  a  very  marked 
reduction  in  the  amount  of  sufjar  present.  Mott  states  that  the 
susjar  is  reduced  in  dementia  ]ira'co\,  but  in  a  series  of  cases 
whi'-h  I  examined  I  did  not  find  this  to  1k>  ihe  case.  It  will  be 
noticed,  however,  that  the  lowest  average  in  Weston's  series 
was  obtained  in  dementia  precox. 

There  is  a  \ery  considerable  increase  in  the  sugar  content 
in  diabetes  mellitus.  With  the  onset  of  diabetic  coma  Ixitli 
diacetic  acid  and  acetone  are  as  a  rule  readily  demonstrable. 
In  ca-es  in  which  the  onset  of  dial)etic  coma  is  feared  it  is 
possible  that  the  api)earance  of  these  substances  in  the  spina! 
tluid  may  be  an  earlier  and  therefore  more  valuable  pro,i,mostic 
sign  than  their  ])re--ence  in  the  urine. 

The  theoretical  interest  of  the  jjrcsencc  of  and  variations 
in  the  ^ugar  in  the  cerebrospinal  fluid  is  great.  The  cere- 
iirospinal  tluid  has  already  I)een  compared  to  Ringer's  fluid, 
in  which  the  function  of  the  sugar  is  to  provide  nourishment 
and  minister  to  the  metabolism  of  the  |)erfused  organ.  The 
sugar  in  the  spinal  tluiil  is  undoubtedly  intimately  concerned 
with  the  metal)olism  of  the  nerve  centers,  and  its  presence  or 
absence  may  be  regarded  as  an  index  of  the  activity  of  the 


CHEMICAL   COMPOSITION 


57 


metal  Mil  ism  which  is  takini,'  place.  The  data  at  our  (lis])osal 
are  not  vet  siifliciently  extensive  to  warrant  us  in  drawing  con- 
clusions regarding  the  behavior  of  the  cerebrospinal  sugar 
in  metabolic  affections  of  the  central  nervous  >^ystein.  but  this 
offers  a  promising  field  for  future  investigations.  It  is  often 
asserted  that  a  fliminution  of  sugar  occurs  in  general  paralysis, 
but  I  have  not  been  able  to  satisfy  myself  that  this  is  the  case. 
The  variation  of  the  sugar  content  in  the  various  forms  of 
meningitis  has  a  simple  exi)lanation.  'Ilie  meningococcus,  the 
pneumococcus,  and  the  streptococcus  all  possess  the  power  of 
readilv  fermenting  glucose.  In  meningitis  duo  to  these  or- 
ganisms, therefore,  the  sugar  is  diminished  or  absent.  The 
tubercle  bacillus  decs  not  i>()>sess  this  power.  1  lence  the  sugar 
is  as  a  rule  little  changed  in  tuberculins  meningitis. 

This  varying  behavior  of  the  sugar  may  be  of  considerable 
value,  both  diagnostic  and  jirognostic.  to  the  physician. 

It  is  one  of  the  bedside  tests  which  may  settle  the  diagnosis 
for  or  against  meningitis.  With  a  frankly  purulent  Huid  the 
need  does  not  arise.  T.ut  in  early  cases  the  fluid  may  bo  opal- 
escent or  even  clear.  In  such  cases  a  marked  disappearance 
of  sugar  would  point  very  strongly  to  meningitis. 

In  the  matter  of  prognosis,  a.gain.  it  may  be  well  worth 
while  to  test  the  I'ehling  reaction.  In  the  course  of  a  ca.se  of 
meningococcal  meningitis  treated  by  injections  of  senini.  re- 
lapses in  the  clinical  condition  may  (Kcur.  These  may  or  may 
not  be  due  to  further  activity  on  the  part  of  the  meningococcus. 
In  the  former  case  the  sugar,  which  has  begun  to  reappear 
with  convalescence,  will  again  disappear,  and  more  serum  must 
1)C  administered.  In  the  latter  the  sugar  will  remain  unaltered, 
and  serum  is  not  indicated. 

In  anterior  poliomyelitis  tlie  sugar  is  not  at  all  reduced. 
This  is  one  of  the  chief  respects  in  which  the  fluid  differs  from 
that  of  tul)erculous  meningitis,  as  far  as  our  present  knowledge 
goes.  The  sugar  of  the  spinal  fluid  should  therefore  always 
l)e  tested  in  suspected  cases  of  poliomyelitis. 


58       IMIVSIOLOGV  AM)   PATMOIO'lY  OF  TUli   ('KRIiBROSI'INAL  FLUID 


: 


UREA 

I'rca  (m.-ur>  in  iln.'  iMnual  txTciiru-Npinal  lluiil  (d  the  cxU'iit 
(if  o.do'i  JILT  ixiit.  It  i>  uui'iuc  aniiinj;>t  the  cuii-titueiits  of 
the  Ihiiil  ill  that  it  iiKTcascs  witli  an  iiicrca>c  in  the  urea  con- 
tent of  tile  1)1(1(1(1.  J)onl)t!ess  this  is  accunnted  for  hy  the 
extreme  dilTnsihility  of  urea,  to  which  no  check  is  placed  hy 
the  epithelium  of  the  choroid  jilexus. 

Ill  true  uriinia,  thai  i>  to  >ay  where  there  is  a  condition  of 
renal  iniperniealiiliiy  to  urea,  the  increase  of  the  urea  content 
of  tho  Iilood  is  c!o-ely  paralleled  hy  a  similar  increase  in  the 
cereliro-pinal  tlnid.  \\  liere.  hn.'.ever,  t!;i;\  is  nurclv  a  re- 
tention of  chlorides  with  a  normal  excretion  of  urea,  sucli 
an  increase  is  no  longer  found.  M;mv  cases  of  cardio-va-- 
cnlar  di-^ease,  etc..  are  wrongly  diarno'-ed  as  clinical  cases  of 
ura'inia.  and  in  >ucli  ca-es  an  e-timalioii  of  the  .'uiiiiunt  of 
urea  in  the  spinal  llnid  is  of  >;reat  v.alne  hotli  in  diaj.,Miosis  and 
proi^nosis. 

The  estimation  of  the  urea  in  the  Mood  i-.  a  little  dilTicult. 
In  the  case  of  the  -piiril  llnid  ii  is  perfectly  simiile.  As  the 
amounts  in  the  two  ca^es  coincide  so  clu-elv,  it  is  evident  that 
a  valualilc  means  i>  ]iro\ide(l  for  (Ktermininj^  the  exi-tence  of 
a  (rue  urea  retention,  a  means  which  will  prove  especially  valu- 
able in  cases  of  coma  of  uncertain  nature. 

Canti  found  that  in  cases  clinically  diaj^nosed  as  ura'mia 
those  with  a  hi^h  cerehrospinal  urea  content  all  proved  fatal, 
whcrea-  those  with  a  low  urea  content  for  the  mo>t  part  re- 
covered. Mestre/at  t;i\es  the  fi,i,aires  in  pure  ura-mia  as  varv- 
inpj  hetueen  f>.0()S  per  cent,  and  ''>f\^\  per  cent.  Those  helow 
0.3  j)er  cent,  were  curalile,  those  alnive  0.3  per  cent,  were  all 
fatal. 

The  hypohromite  method  is  sufhcient  for  clinical  imrposes. 
Five  c.c.  of  cerehrnspinal  fluid  are  mixed  with  j;  ex.  of  .(o 
per  cent,  potassium  hydrate  solution,  to  which  ;m  ampule  coii- 
tainin;:^  2.2.  c.c.  of  hromine  is  added.  The  results  can  lie  read 
in  the  u.siial  way.  The  ammonium  salts  .and  other  suhstances 
which  interfere  with  the  accuracy  of  tliis  method  in  the  case  of 


CHEMICAL   COMPOSITION 


59 


the  urine  are  of  course  not  met  with  in  the  spinal  fluid.  For 
mole  accurate  work  it  is  best  to  use  the  urease  method  of 
Marshall.  This  is  carried  out  in  exactly  the  same  way  as  in 
estimations  of  blood  urea. 


ki;|'KRi:x(;ks 

("ami,  K.  <"■.:  Tlio  urea  couleiit  of  the  ccrcbros])inal  fluid, 
Lancet,  1916,  I.  p.  344. 

1  lori'man.  W.  (»  .iiid  Schwartz,  A.  I'..:  The  potassium  i)crmaii- 
Vfaiiate  reduction  index  of  the  cerebrospinal  fluid.     .\rch.  Int.  Med., 

1<;|6,    Wll,    p.    2()3. 

Jiims.  I"..:  'ilie  ))n)lein  content  of  cerel)rospinal  fluid  in  j,'entral 
par.ily^is.      I\ev.  of   Xeiirol.  and  I'sych.,    l<)0<).  |).  379. 

Myirs,  \'.  I'.  ,111(1  I'lailey,  (".  \'. :  The  [.cwis  and  I'enedict  metIio<l 
for  the  estimation  of  hlnoil  suijar,  with  some  observations  obtained 
in  disease.      Four.  I'.iol.  (hem.,  ]i)\C),  .\XI\',  p,  147. 

r'"iiinc  and  .\pelt :  Cber  l'"raktioiiertc  luwcissausfidlung  in  der 
Spiii.ilfliissitrkeit.  etc.     .\rch.  f.  I'.sychi.at.,   I0"7,  I'd.  XI.llI,  II,  2. 

I'andy:  I'ber  cine  iieiie  F.iwcissprobe  fiir  die  Zcrebrospinalfliis- 
siRkeit.     Xeurol.  Centralhl.,  i<)io,  p.  Qi.'^- 

Weston,  1'.  I"..:  .^ni;ar  content  of  the  blood  and  spinal  fluid  of 
insane  subjects.     Jour.  Med.  Research,   i<)ifi,  XX  W,  p.   i<)i). 


( ii.\i'ri:u  \ 

c  \  TOl.CXiV 

Ilk-  iiMrmal  ctTclini^piii.i!  lliiiil  contain-!  ;ni  occasional 
K  ni]ili  i  s  It  .ithl  ''nuiMnc-  an  iiidolliclial  cell  or  two.  in  (li>- 
ca-c  C'lniliti'ii!-,  i\'IU  uiaKo  llicir  appearance  in  varyinjj  nniu- 
liiT>.  It  i-  II'  !  I'iily  tile  ir.inilar  which  \aric>.  Tin.'  cell  t\pe 
>lio'.\^  an  ei|ii,i!I'  L;rcal  i.iriation.  \lino>t  any  Mood  cell  may 
lie  present  in  addition  lo  a  coii -idcralile  \ariety  of  ti-isne  cells. 
Too  little  .:lte!Ui"n  '  i-  Imii  paid  I  ■  the  particnlar  l-iml  of  cell 
]ire-ii!l  in  dilTercni  piitholo^ical  Conditiniw.  llow  often  do  \vc 
ri'a'l  ih.i'  c\  t  -i-  wa-  fo;mi|,  a  pleoi yi^ ■-!<.  an  increa-cil  cell 
C'luni.  .i:o\;t  a  wonl  a-  t"  tin-  natnre  of  tlii'  celN.  Our 
I'e^i'n'      no 


\   ri  c.    rin' 
.•qipear     i  •' 
ci-rehr'  > 
"athi'l. 
n'  irm.d 
''•f  i:-n      Mi 

■nc  —  ! 
te.' 

I  ,inai 

!io|!  mtii 


!■/'■  if  di-i'a>t'<  (if  the  Mood  lia>  heen  ;,'ained 

!eivniiil    Mniy  of  the  vaiion^  cells  which  may 

Snnilar  -tndy  i>  needed  in  the  <'a>e  of  the 

d  if  We  are  !  ■     'itain  :\  ti"ne  CMnci-ption  of  the 

n\    ■  •'   llie   n  ndii:    '.' ■   in   which   it    shows  ah- 

'I'lii     nc'derl    i-  pariK    dne  to  the    t'.ict   that 

K      '"     •II  (  \aini'i,i!ion  are  inadt"|nate  lor  pnr- 

'Ure-       lion,  am!  that  the  oiu-  really  excellent 

:    \      tinier —  )>  <oniewhat  cninhersonie  and 

ell>  of  the  cereliro-.]iinaI  t1ni<l  nin-t  he 
lalitatixe. 


i 


QU*VTITATIVE  EXAMINATION 

The  French  method.  It  was  the  iin  estii^^ations  of  W'idal, 
Sicard  and  l\a\ant  in  looi  npon  the  cell  content  of  the  spinal 
tlnid  which  fir-t  drew  attetttion  to  the  clinic;il  importance  of 
the  llnid.  ;ind  it  wa-  therefore  inlnr.al  that  their  method,  com- 
tiiiiiilv  cilled  tile  I'rcnch  melhud.  -hoiild  have  heen  n-ed  Iv  the 
earlier  workers.  I.atterlv.  however,  it  h;is  fallen  into  disnsf 
and  almost  into  a  disrepute  which  is  certainly  undeserved.     For 

fio 


CYTOLOGY 


6l 


by  it  an  idea  as  to  wlictlur  a  pathological  increase  in  the  cells 
is  present  may  Ik-  gained  (|uite  as  accnrately  as  hy  the  ordinary 
li.eniocytonietcr,  althoiij;h  not  with  the  same  accuracy  as  is 
given  hy  the  methiKl  of  I'uchs  and  Rosenthal.  I'urtiier,  a  rea- 
sonably good  picture  of  the  variety  of  cells  present  is  afTordeil. 
The  technic  demamls  a  reasonalile  amount  of  care. 

Ii\e  cuhic  centimeter--  of  spinal  lluid  are  placed  in  a  taper- 
ing centrifuge  tuK",  which  must  he  scrupulously  clean,  and  cen- 
trifuijed  at  a  rapid  rate  —  i  joo  rcvelulinns  ptT  miiuilc —  for 
half  an  hour.  The  llnid  is  decanted  and  the  tulic  allowed  to 
stand  upon  Motting  paper  in  an  inverted  position  for  t,  min- 
utes, so  that  onlv  a  trace  of  lluid  remains  in  the  tuhe.  'I'he 
tul»e  is  then  returned  to  the  U])right  position,  and  when  not 
more  than  a  drop  of  llnid  h.is  made  its  apjioarancc  at  the 
hottom,  the  sediment  is  taken  u])  into  a  fmc  c;i])ill;iry  tulie  ;i:id 
hlowii  out  on  to  a  glass  >!ide.  This  is  the  ]i:irt  of  tiie  pro- 
cedure which  rei|uires  care  and  ;i  certain  degree  of  ^kill.  The 
.same  capillary  should  i>e  used  each  time.  If  treated  reason- 
ahlv  its  life  will  he  a  long  one.  Xot  more  than  a  small  dro|) 
of  lluid  mu^t  he  allowed  to  collect  at  the  bottom  of  the  centri- 
fuge tube,  otherwise  the  sediment  will  be  unduly  diluted. 
The  capillarv  should  be  twirled  anmnd  the  bottom  of  the 
tube  in  order  that  no  sediment  may  be  left  adhering  to  the 
walls.  I'in.illy  the  lluid  nnist  not  be  blown  out  of  the  ca- 
pillary all  over  the  slide.  Hlow  geiuly  luitil  a  drop  ai)i)ears 
hanging  from  the  end  of  the  capillary.  Then  touch  the  slide 
gently  with  the  drop,  taking  care  that  the  latter  docs  not  .spread 
out  upon  the  slide.  L'nless  this  precaution  is  observed  the 
count  will  be  too  low.  The  drop  of  lluid  is  dried  in  air, 
fixed  in  absolute  alcohol  for  lo  minutes,  and  stained. 

'ihe  count  is  made  by  examining  the  slide  under  a  magnifi- 
cation of  450  diameters  —  high  power  —  and  taking  the  av- 
erage of  a  numlxT  of  fields.  It  is  advisable  to  count  at  least 
to  fiehls,  and  these  should  include  both  the  margin  and  the 
center  of  the  dro]),  for  the  cells  tend  to  Ik.'  collected  more 
denselv  at  the  former  than  at  the  latter. 

if  details  of  the  technic  Ik-  atteiuled  to  the  French  method 


<i2        PIIVSIOI.O<;Y  AND   PATIIOI.OT.Y  OF  TIIK  CERKBROSPINAI.  FLUID 

will  ]tc  found  til  j,Mvi-  ci mutant  and  accurate  rcsidts.  Sonic 
years  ai;o  1  tested  it  in  a  >eiies  of  ol»er\ations  on  tlie  cereliro- 
•-pinal  fluid  of  tlie  insane.  I  lie  patient-,  were  not  reeeiuti;; 
any  special  treatment  and  tlie  condition  of  their  lluitl  nii.L^lit 
tlierefore  le  reL;;irded  a>  rea-onahly  coii>!ant.  In  a  eoii>id- 
eralile  nnnilier  of  ea-i'^  tlie  lluid  was  examined  on  -everal  o,-- 
ca>ions  and  the  re-nit>  were  remarkaMy  constant.  1  am  con- 
vinced that  the  xarialiMii  w.mld  lia\e  heeii  fully  as  j^reat  and 
prohahlx  L'Teater  with  the  ordiniry  Ii.eni 'cylonieter  method. 
In  addition  the  method  pro\  ides  a  |)ermanent  ]ireparation.  and 
enalile-  a  dillVreiitial  count  to  he  made. 

Variolic  niddirn-.ition-  of  the  ori^in.a!  i'reneli  nuihod,  <uih 
as  those  of  Xissl.  and  I'"ischer  and  Kafka,  have  heen  from 
time  to  tinu-  inirudiued,  hut  tlu'\-  .are  not  of  sutiuient  import- 
ance to  lie  Coll  idered  in  detail. 

The  counting  chamber  method.  r>eful  a>  the  hreiich 
method  undoulitedly  i>.  there  can  he  no  duulit  that  the  he>t  all 
nmnd  method  nf  cell  e-tini:Uion  i-~  the  ti-e  i.f  the  >i)eii.d  count- 
in;,' chamher  of  l"iieh.,in(I  lv'-(.nlli.d.  I'nfortun.ilely  in  m.iny 
in--tanees  the  -^peeial  eh.imlii.r  i-  not  ;iv:iilali|e.  with  the  result 
that  the  ordinary  'riioin.i-Zi'i^^  .ipp.iratiis  is  u-eil. 

The  Thoma-Zeiss  chamher  is  i  mm.  square  and  o.  i  mm. 
deej).  The  total  volume  is  therefore  I  id  e.iiini.  The  I'uehs- 
Roscnthal  ehaniler  on  the  otlier  hand  is  \(>  mm.  s  |uare  anil 
O.J  mm  deep,  with  a  re^ultini,'  c,i]i.uity  of  ifi  ;  e.  mm.  or 
ahout  _^  c.nim.  The  numlier  of  cells  counted  is.  therefore, 
very  much  j;reater.  .and  the  marL^Mii  of  rrror  enrresjioudinj^dy 
less. 

The  cerehro^iiin.al  lluid  which  ^hmild  he  as  fre^h  as  pos- 
.sihle  is  well  shaken  up  so  as  to  ensure  a  uniform  distrihution 
of  cells.  I'-iim  an  ordin.irv  white  .'ell  countiiif^'  pipette,  stain 
is  drawn  u\>  to  the  mark  i,  and  cere1iro>.pin,d  lluid  to  the 
m.ark   i  i.       i'lie  ^l.iiuini;  Huid  ciu-'i-ts  nf :  — 


Methyl    violet    o.  i 

(ilaeial  acetic  acid J.o 

Aq.   (lest 50.0 


CYTOl.OC.Y 


f'i 


After  .illowiii},'  llu-  >taiii  to  act  for  a  l\u  miimtcs  a  drop 
of  tluid  is  plaii'd  on  the  counting'  cliamlaT  an<l  the  cells  arc 
CDiiiiteil  ill  the  onlinary  iiiaiiiier.  This  j,'ivcs  the  number  in 
ifi  5  c.  tniii..  ami  hy  div  idiii;;  hy  three  the  nunilier  per  c.  mm. 
is  olitaiiied.  \\  ith  practice  a  fair  i<lea  as  to  the  type  of  the 
cell  prc>eiit  may  lie  olitaiiied.  for  the  cells  have  inider;;one  none 
of  the  distortion  which  is  liahle  to  cicciir  diirin.i,^  the  priK'ess 
of  drvin*,'  in  the  hrench  method,  lint  at  tirst  cell  dilTerentiation 
will  he  fonml  a  matter  of  coii-iderahlc  dirficnlty. 

The  iMichs-Ko^enthal  method  has  received  a  thorough  test- 
ini,'  durint;  the  la-^t  do/en  years,  and  it  may  safely  he  said 
that  it  is  fiitilr  priihr/'s  anion:,'  methods  of  cell  coimting. 
(  )ne  of  its  i^rcat  ailvantai,'e>  is  that  the  smallest  quantity  of 
llnid  will  snOice.  'i'his  is  a  point  of  coiisideraMe  importance 
in  such  conditions  as  tumor  of  the  hrain  where  the  withdrawal 
of  ;uiv  larue  amount  of  lliiid  may  he  i|uile  inadmis>ilile. 

Another  ijreat  practic  d  advantaj,'e  is  that  it  can  he  carried 
out  at  the  licdside.  Indeed  the  sooner  the  count  is  made 
after  withdrawal  of  the  lluid  the  hetter,  as  sedimentation  oc- 
curs rapidiv,  ami  the  cells  are  lialile  to  adhere  to  the  sides 
of  the  tuhe. 


THE  CELL  COUNT 

Whatever  method  ho  used,  the  interpretation  of  the  find- 
injjs  is  of  primarv  importance.  A  normal  and  a  pathological 
limit  can  K-  fiNcd,  hut  hetwecn  these  two  there  comes  a  Ixiun- 
darv  zone  in  which  the  laboratory  finditif^s  mn^t  he  read  in  the 
lip;ht  of  the  clinical  facts.  The  nnmlnMs  in  the  French  and 
cotnitin.c;  chaniltcr  methods  correspond  closely.  Prom  i  to  5 
cells  per  c.  mm.  or  in  an  averac^e  field  may  he  taken  as  normal, 
and  anvthini;  .above  in  cells  as  abnormal.  Tiefween  thc'^e  there 
is  the  l)oundarv  or  indefinite  xone,  in  which  a  definite  opinion 
can  often  not  be  expressed.  Tn  such  cases  it  may  be  wise 
to  perform  a  second  jiuncture  a  dav  or  two  later. 

The  hitrhe<t  counts  are  obtained  in  acute  suppurative  men- 
in;:itis.  in  which  there  may  be  many  thousands  of  cells  per 
c.  mm.     Farlv  cases  of  tabes  dorsalis  and  sfcneral  paresis  may 


MICROCOPY    RESOIUTION    TEST   CHART 

ANSI  cipd  bO  lESI  CH    ?I  No    2 


1.0 


I.I 


IIM 

m 
m 


m 

2.2 

ZO 

1.8 


!l-25   iu 


1.6 


^     ^r  ^LIED  IN4^GE 


64        PHYSIOLOGY   ANU    PATHOLOGY   OF   THE  CEREBROSPINAL  FLUID 

give  a  count  of  a  luiiulred  or  more.  As  the  disease  progresses 
tlie  count  tends  to  fall  and  in  advanced  cases  of  paresis  it  may 
not  lie  more  tlian  lo  (,r  jo.  An  ordinary  case  of  talx.'s  as  a  rule 
gives  a  count  of  under  loo.  hut  often  the  figure  is  very  much 
smaller.  Active  cerebrospinal  syphilis  especially  the  meningi- 
tic  form  is  sometimes  associated  with  an  extremely  high  count, 
in  some  cases  there  being  several  thousand  cells  present.  In 
that  form  of  tlie  disease,  iiouever.  in  which  endarteritis  is  the 
chief  feature  there  may  be  little  or  no  pleocytosis.  One  of  the 
most  constant  signs  of  tuberculous  meningitis  is  a  cerebro- 
s])inal  lymphocytosis,  often  I)etween  loo  and  joo.  but  in  some 
cases  so  low  as  tn  cause  grave  doubt  regarding  the  diagnosis. 
In  the  earliest  stages  t)f  poliomyelitis  there  is  a  constant 
pleocytosis,  and  a  moderate  increase  may  occur  in  encephalitis 
lethargica. 

.\n  increase  in  cells  may  thus  occur  in  the  following  condi- 
tions: acute  supi)urative  meningitis,  tuberculous  meningitis, 
acute  anterior  ixiliomyelitis,  encephalitis  lethargica,  general 
])are-is,  tabes,  cerebrospinal  syphilis,  cerebral  abscess,  cerebral 
haemorrhage,  cerebral  tumor  (rarely  and  only  when  cortical), 
herpes  zoster,  mumps,  sleeping  sickness,  cysticercus  cellulose  of 
the  centnd  nervous  system,  and  in  certain  mental  conditions 
which  will  be  di--cusse<l  later.  I'rom  this  brief  survey  it  will 
be  seen  that  a  marked  pleocytosis  is  a  sign  of  great  diagnostic 
value,  but  that  liurderline  results  must  be  accepted  with  caution, 
and  are  to  be  interpreted  in  the  light  of  the  clinical  findings. 

It  is  III  it,  however,  in  diagnosis  alone  that  (observations  on 
the  cell  cnunt  are  of  v.ilue.  As  an  index  to  ihe  success  of 
treatment  they  are  often  inxaluable.  '("lie  pleocytosis  is  the 
first  of  the  pathologic'd  sign-;  to  give  way  to  treatment  in 
cerebr(isi)inal  syjohilis,  and  in  meningitis  the  behavior  of  the 
cells  mav  have  great  prognostic  iiuportance. 


i 


CELL  DIFFERENTIATION 

It  ha^  ,-dreadv  been  remarked  that  sufficient  importance  has 
lint  been  .ittached  to  the  differential  study  of  the  various  kinds 
of  cells  present.     This  is  largely  due  to  difficulties  of  technic. 


CYTOLOGY 


65 


The  ordinary  method  of  drying  a  film  in  the  air  and  staining 
only  gives  diffennitiation  sufticient,  as  a  rule,  to  distinguish 
between  the  polymorphonuclear  and  the  lymphocytic  series 
of  cells.  It  shows  none  of  those  cell.>  upon  the  recognition 
of  which  depends  future  progress  in  such  (|uestions  as  tlie 
mechanism  of  meningitic  inilamniation  and  the  origin  of  the 
new  cells. 

l'"or  this  finer  work  of  differentiation  more  refined  methods 
are  needed.  In  the  Alzheimer  method  we  have  the  method 
suited  above  all  others  for  this  particular  purpose.  It  is  not 
a  Ijedside  method,  but  if  time  and  facilities  are  available,  it  is 
(juitc  une(|ualed. 

The  principle  of  the  method  is  to  precipitate  the  alliumcn 
of  the  lluid  with  alcohol.  The  cells  are  drawn  down  with 
the  precipitate,  and  the  resulting  coagulum  treated  as  a  tissue 
and  cut  in  celloidin.  The  cells  are  instantaneously  fixed  in  the 
fluid,  with  no  opportunity  for  becoming  dried  and  distorted, 
as  in  the  French  method.  The  resulting  cell  picture,  if  the 
section  is  a  good  one,  is  remarkab'°  for  its  variety  and  clear- 
ness. 

From  3  to  5  c.c  of  cerebrospinal  fluid  are  mixed  with  an 
equal  quantity  of  96  per  cent,  alcohol  as  soon  after  withdrawal 
of  the  fluid  as  possible.  If  the  albumen  be  much  increased  a 
dense  chnul  will  form.  If,  however,  there  be  no  increase  it 
is  well  to  add  a  small  amount  of  white  of  egg  solution  to  the 
fluid  in  order  to  obtain  the  necessary  precipitate.  The  tube 
is  then  centrifuged  at  a  high  speed  lor  an  hour,  by  the  end 
of  which  time  a  firm  circular  coagulum  will  have  formed  at 
the  bottom  of  the  tube.  Scattered  throughout  this  coagulum 
are  the  fixed  cells.  The  tluiil  is  decanted,  and  the  coagulum 
hardened  with  absolute  alcohol,  alcohol  and  ether,  and  pure 
ether.  It  is  best  to  allow  each  of  these  reagents  to  act  for 
24  hours,  but  if  time  be  a  consideration  a  few  hours  may 
suffice. 

When  the  ether  has  been  decanted  it  will  prol)ably  be  found 
that  the  hardened  coagulum  has  shrunk  slightly  from  the  sides 
of  the  tube,  so  that  it  is  possible  to  detach  it  from  the  bottom 


66       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


11 


by  means  of  a  platinum  loop  or  a  very  fine  glass  rod.  This 
manipulation  reciuires  care  and  varies  consideraldy  in  dilli- 
culty.  In  many  cases  a  mere  tap  on  the  bottom  oi  tlic  tuljc 
may  suffice  to  remove  the  coagulum.  In  other  cases,  however, 
it  is  so  soft  that  it  is  almost  impossil)le  to  detach  it  without 
causing  serious  damage.  I  have  found  the  !,Teatest  trouble 
in  purulent  fluids  in  which  the  coagulum  although  very  lari;e 
mav  be  extremely  soft.  In  such  a  condition  as  tabes,  on  the 
other  hand,  the  coagulum  is  firm  and  compact  and  very  easy 
to  manipulate. 

The  detached  coagulum  is  shaken  out  into  the  palm  of  the 
hand,  and  placed  first  in  thin  and  then  in  thick  celloidin.  It 
should  be  left  in  each  solution  for  at  least  three  days,  but  may 
with  advantage  remain  much  longer,  l^nally  it  is  mounted 
on  a  wooden  block,  covered  with  thick  celloidin,  and  cut  on 
a  Jung  microtome.  The  celloiilin  is  removed  with  absolute 
alcohol  and  etiier  and  the  sections  passed  through  So  per 
cent,  alcohol  and  distilled  water  into  Pappcnheim's  pyr- 
onin-methyl  green  stain.     This  has  the  following  composition: 

Pyronin   0.J5 

Methyl  green 0.30 

-Alcohol  (/)  per  cent.   .  .  .  2.50 

Cdycerin 20.00 

Carbolic  acid  5  per  cent.  100.00 

The  sections  are  kept  in  this  stain  in  the  water  batli  at  40"  C 
for  5  minutes.  Excess  stain  is  removed  with  distilled  water. 
Differentiate  in  absolute  alcohol  till  no  more  stain  comes 
away.     Clear  in  xylol  and  mount  in  bal.sam. 

Pappcnheim's  stain  is  a  difficult  one  to  ])repare,  and  I  have 
found  it  preferable  to  work  with  the  preparation  sn]>])!ieil  by 
Griibler.  Unna's  polychrome  methylene  blue  gives  an  excel- 
lent picture,  but  with  it  the  cells  do  not  show  some  of  the 
differential  characteristics  obtained  with  the  Pappcnheim  stain. 


CYTOLOGY 


67 


THE  NATURE  OF  THE  CELLS 

With  the  French  method  it  is  not  as  a  rule  possible  to  do 
more  than  differentiate  between  the  polymorplionuclear  cell, 
the  small  lymphocyte  and  the  large  lymphocyte.  By  Alzheim- 
er's method,  however,  cells  can  be  distinguished  which  were  not 
formerly  known  to  occur  in  the  cerebrospinal  fluid.  In  such 
a  condition  as  general  paresis  the  variety  of  cells  may  be  truly 
bewildering.  Indeed  there  is  a  tendency,  especially  on  the 
part  of  German  writers,  to  multiply  types  and  names  to  an  ex- 
tent which  it  is  very  improbable  that  future  work  will  justify. 

Tlie  lymphocyte  is  the  most  important  cell  in  the  spinal 
fluid.  In  health  it  is  the  only  variety  besides  the  endothelial 
cell  which  is  found.  In  subacute  and  chronic  inflammations 
of  the  meninges  any  increase  of  cells  is  mainly  confined  to  the 
lymphocytes.  Tuberculosis  and  syphilis  afford  examples  of 
such  conditions. 

The  typical  lymphocyte  is  a  compact  little  cell  rather  smaller 
than  a  red  blood  corpuscle.  It  consists  mainly  of  a  nucleus. 
The  nucleus  stains  ir.tensely  blue  with  Tappenhein's  stain  and 
shows  a  very  characteristic  peripheral  or  clock-face  concentra- 
tion of  the  chromatic  sul)stance,  although  this  appearance  is 
not  so  marked  as  in  the  plasma  cell.  The  cytoplasm  is  scanty, 
forming  a  narrow  rim  round  the  nucleus,  and  stains  pink  or 
red  with  pyronin.  Some  of  the  cells  may  be  larger  than  a 
red  blood  corpuscle,  and  may  then  be  called  large  lymphocytes. 

In  disease  conditions  associated  with  increase  in  the  number 
of  lvmphoc\tes  it  is  coinmon  to  meet  witli  cells  which  stain 
poorly.  These  are  probal)ly  lymphocytes  which  arc  under- 
going degeneration,  and  are  no  longer  able  to  take  up  the 
basic  stain.  In  a  fresh  case  of  meningeal  irritation  almost 
all  the  cells  take  up  the  stain  in  the  normal  manner.  -After  a 
nnmber  of  weeks  have  elapsed,  however,  large  numl)crs  of 
these  feebly  staining  degenerating  cells  may  make  their  ap- 
pearance. They  may  be  regarded  as  cells  whicli  have  passed 
the  hey-day  of  their  youth,  and  are  now  in  a  condition  of 


I 


68       PHYSIOLOGY  AND  PATHOLOGY  (  F  THE  CEREBROSPINAL  FLUID 

senility.  In  some  cases  of  lymphocytosis  the  cytoplasm  of 
certain  of  the  lymphocytes  is  elongated  in  one  direction,  giv- 
ing what  has  been  called  a  tailed  appearance  to  the  cells.  It 
is  doubtful  what  importance  .should  be  attached  to  this  pe- 
culiarity, or  whether,  as  has  been  done,  the  cells  should  be 
placed  in  a  separate  group.  The  condition  in  which  tailed 
lymphocytes  are  most  abundant  is  new  growth  of  the  brain. 
In  this  condition  they  may  outnumber  the  ordinary  form  of 
lyniph()c\te. 

The  endothelial  cell  can  readily  be  distinguished  from  the 
lynii)hocyte.  It  is  larger  and  the  nucleus,  which  does  not 
take  on  the  intense  stain  so  characteristic  of  the  lymphocyte, 
is  placed  somewhat  eccentrically  and  is  usually  indented  or 
kidney-shaped,  although  in  some  cases  it  may  be  spherical. 
The  nucleus  docs  not  show  the  clock-face  arrangement  of 
chromatin  granules.  It  is  probable  that  these  cells  originate 
from  the  lymph  cells  in  the  pia  mater.  In  general  paresis 
they  are  often  present  in  considerable  numbers,  averaging 
aljout  lo  i)cr  cent,  of  all  the  cells.  This  figure  may  1^  more 
th;ui  douliled  in  p()-.l-nu)rlcm  lluids  (Cotton  and  .\yer). 

Polymorphonuclear  cells. —  It  is  sometimes  stated  that  the 
polymorpli  may  occur  in  normal  fluid,  but  I  have  never  met 
with  one.  except  in  cases  in  which  there  was  blood  contamina- 
tion. With  Pappenheim"s  stain  the  nucleus  alone  is  visible. 
In  order  to  demonstrate  the  cytoplasm  it  is  best  to  make  a 
film  and  stain  it  with  one  of  the  Romanowsky  stains.  In  acute 
p  irulent  meningitis  there  may  be  enormous  numbers  of  poly- 
morphs, to  the  exclusion  of  all  other  cells.  In  tuberculous 
meningitis  the  proportion  varies  greatly,  depending  partly  on 
the  acutcness  of  the  condition.  As  a  rule  they  are  greatly  out- 
nuinl)ere(l  by  the  lymphocytes,  but  occasionally  the  preponder- 
ating cell  may  be  the  polymorph.  These  cells  are  present  in 
small  numbers  in  general  jiaresis.  In  acute  exacerbations  of 
the  disease,  and  es])ecially  after  convulsive  seizures,  there  may 
be  a  marked  increase,  the  proportion  sometimes  reaching  50 

per  cent. 

The  supremacy  of  the  polymorph  in  acute  meningitis  only 


CYTOLOGY 


69 


holds  for  the  early  and  acute  stages.  As  improvement  sets 
in  lymphocytes  and  endothelial  cells  make  their  appearance 
and  eventually  replace  the  polymorph  completely.  In  one 
case  of  meningococcal  meningitis  the  polymorphs  at  first 
numbered  96  per  cent.  After  some  weeks  of  serum  treat- 
ment the  number  fell  to  50  per  cent,  and  when  the  patient 
finally  recovered  they  had  entirely  disappeared,  although  there 
remained  considerable  numbers  of  lymphocytes  and  endothelial 
cells. 

Plasma  cells. —  The  plasma  cell  is  larger  than  the  lympho- 
cyte and  of  very  characteristic  appearance.  It  is  rounded 
or  polygonal,  often  presenting  a  tailed  appearance.  The 
nucleus  is  as  a  rule  markedly  eccentric,  stains  intensely 
blue,  and  the  clock-face  arrangement  of  its  chromatin 
is  even  more  marked  than  in  the  lymphocyte.  The  cytoplasm 
which  is  coarsely  granular  stains  an  intense  red  with  pyro- 
nin.     Indeed  Pappenheim's  stain  i3  specific  for  these  cells. 

The  presence  of  plasma  cells  in  the  perivascular  cellular  in- 
filtration in  the  brain  in  general  paresis  is  well  known,  but 
they  had  never  been  found  in  the  cerebrospinal  fluid  until 
the  introduction  of  the  Alzheimer  method  made  it  possilile  to 
demonstrate  them  in  nearly  every  case.  At  first  it  was 
claimed  that  these  cells  were  absolutely  pathognomonic  of 
general  paresis,  but  this  position  can  no  longer  be  maintained. 
Rehm  and  Hough  have  found  them  in  cerel)ral  syphilis,  and 
Henderson  in  tabes  dorsalis  and  tuberculous  meningitis. 
They  are  therefore  not  typical  of  any  one  condition,  but  they 
have  never  been  found  in  the  normal  fluid. 

Gitterzellen  or  lattice  cells.—  These  arc  the  largest  cells 
found  in  the  fluid,  being  at  least  10  times  as  large  as  a  lympho 
cvte.  The  nucleus  is  large,  usually  eccentric  in  position,  and 
docs  not  stain  very  deeply.  The  cytoplasm  is  faintly  stained 
and  shows  the  characteristic  vacuolation  or  lattice  work. 
Perhaps  the  cytoplasm  may  l)est  l)e  described  as  Iieing  foam- 
ing in  appearance.  In  some  cases  it  a]ipcars  to  1)e  converted 
into  one  great  vascuole,  and  presents  no  structure  whatever. 
These  cells  are  never  met  with  in  the  normal  fluid.     They  are 


70       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

very  characteristic  of  f^a-nc-ral  paresis,  hut  have  also  heen  foind 
in  tiihcrciilons  meningitis. 

Phagocytes. —  In  a  variety  of  niorhid  conditions  it  is  com- 
mon to  find  large  cells  with  cell  inclusions.  It  is  dilVicuU  to 
know  whether  these  cells  deserve  to  he  groujied  in  a  separate 
class.  It  may  well  he  that  they  are  merely  en  lothelial  cells 
which  have  taken  on  a  phagocytic  funi-tion.  The  cell  in- 
clusions arc  generally  degenerated  lymphocytes  or  red  hlood 
corpuscles. 

Fibroblasts. —  A  sharply  deHned  and  characteristic  variety 
of  cell  is  the  tihrohlast,  which  occurs  in  small  ntimhers  in 
syphilitic  infections  of  the  central  nervoin  system.  It  is  a 
narrow  elongated  cell  similar  in  appearance  to  the  lihrohlast 
of  connective  tissue.  The  nucleus  is  elongated  and  stains 
somewhat  faintly.  The  cytoplasm  stains  moderately  deepl}- 
with  pyronin. 

Many  other  sulivarielies  of  cells  have  heen  named  and 
classified,  notahly  hy  ."^zccsi,  who  speaks  of  microlymphocytes. 
microlymphoidocyte-.  lymi>hoidocytes.  plasma  datighter  cells, 
etc.  Until  our  cytological  knowledge  is  more  .-'.dvauced,  how- 
ever, such  minute  suhdivision  only  tends  to  confusion,  and 
serves  no  useful  purpose. 

ORIGIN  OF  THE  CELLS 

Xo  hetter  exatuiile  of  the  diametric;illy  i>i)posed  \iew^  which 
are  still  held  on  many  points  regard'ug  the  ccrelirospinal  Ihiid 
could  he  afforded  than  the  (|ue<tion  of  the  origin  of  its  cells. 
The  two  extremes  are  represented  hy  Pappcnheim.  hohling 
that  all  the  cells  come  from  the  Mood,  and  S/ecsi.  who  main- 
tains that  thev  are  almost  all  derived  from  the  tissue^. 

As  so  conmionlv  f>ccurs  in  the  histc^y  of  science,  it  is 
prohaMe  that  the  truth  lies  midway  hetween  these  extremes. 
Tt  is  ohvicnis  that  certain  cell-^  mu-t  he  Irematogenoiis  in  origin. 
Tn  a  case  of  acute  ])urulent  meningitis  the  Ihiid  is  practically 
converted  into  pu^.  The  cnonnMus  mimhers  of  pilymor- 
phnnuclcar  ]cuc<>c\ic-  v,hich  it  '.-ontnins  can  certainly  oric:'nato 
from  nowhere  hut  the  hlood.     In  response  to  an  acute  irritant 


CNTOLOGY 


7> 


the  vessels  show  the  usual  phenomena  of  inflaniniation.  and 
eniif^ration  of  leucoiytes  takes  place  just  as  in  the  case  ot 
acute  inllaiuniatiou  elsewhere. 

The  same  is  true  for  eosinophil  leucocytes.  Cases  have 
been  descrihed  of  cy.-ticercus  cellul()>:e  iniectiiu  of  the  central 
nervous  system  in  which  th.en.'  was  a  markdl  eosin,)phiIia  Imth 
in  the  I)lood  and  in  the  ccrehrospin.-d  lluid.  Whatever  he  the 
true  relation  hetween  infectit^n  by  animal  parasites  and  the 
appearance  of  an  increased  number  of  eosinophils,  there  is  no 
reason  to  suppose  that  the  eosinophils  in  the  spinal  fluid  have 
been  derived  from  any  other  source  than  the  blood. 

On  the  other  hand  it  by  no  means   ictllows  that   because 
certain  of  the  cells  undoulitcdly  originate  from  the  blood,  all 
the  cells  must  have  a  similar  orit^in.      In  i.rder  to  recoi:;nize  the 
importance  of  a  histoj^enous  source  it   is  i,  ily  necessary  to 
examine   sections    of    brain    frotn    such   diseases   as    iL^cneral 
paresis  and  sleeping  sickness.     In  both  of  these  conditions  the 
perivascular  space  in  the  affected  areas  is  crowded  with  cell.s, 
mainly    lymphocytes    and    plasma   cells.     'I'he^e    have    arisen 
from  the  fixed  cells  of  the  tissue  in  response  to  the  action  of 
a   chronic   irritant.     They   stand   in   intimate   relation  to  the 
perivascular  prolon.!:,'ations  of  the  subarachnoid  space.     '1  hese 
tissue-derived  cells  have,  therefore,  the  readiest  access  to  the 
cerebrospinal  tluid,  and  in  conditions  in  which  they  undergo 
a  pathological  increase  in  number  it  would  indeed  be  .surpris- 
ing if  they  did  not  make  their  appearance  in  the  lluid.     The 
endothelial  cells  are,  I  believe,  derived  from  the  endothelial 
lining  of  the  perivascular  lymphatics.     The  fibroblasts,  again, 
are  cells  which  can  have  but  one  origin,  namely   from  the 
tissues. 

In  discussing  this  question,  however,  there  is  one  point 
which  must  not  be  overlooked.  Cells  passing  from  the  blood 
into  the  cerebrospinal  fluid  find  themselves  in  a  very  different 
environment,  and  considerable  changes  of  an  adaptive  or  de- 
generative nature  may  occur  in  their  morphology,  so  that  they 
may  lose  all  resemblance  to  their  former  selves.  This  is  a 
point  deserving  of  further  investigation. 


72       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLVID 


RKIT-RKXt  KS 

Alzheimer:  l".ini«:e  Mctlmdcn  ziir  I'iniiriinf?  dcr  zetliRcn  Elemcn'c 
der  Zerebrosiiinaltliissigkcit.  ZcntralM.  f.  Xervcnh.  n.  Psycl'. 
1907.  N.  239. 

I'olton  n.  A.  and  Aver  J.  I'..:  Tlie  cytnlosical  examination  of 
the  cerelimspinal   thiid.     Jour.   Xcrv.  and  Ment.   Dis.    lyiX.  XXXV, 

I'-  ?.')')■ 

Inichs  and  Roscntlial:  l'h>Nii<ali>chc,  chcmischc.  zytolo-ischc 
iind  andcrwcitijjc  Untersuchungen  tier  Zcrebrospinahliis-ii^koit. 
W  fin.  nicd.  Pressc.,  1904,  X.  44-47. 

Henderson  I).  K.  and  Muirhcad  Winifred:  The  differentiation  of 
cells  in  tlie  cerebrospinal  fluid  by  the  .Mzheinier  method.  Rev.  N'eu- 
rol.  and  Psych.  1913.  XI,  p.  195. 

Hough  \V.  H.:  The  cytological  examination  01  the  cerebrospinal 
fluid.     Pull.   Xo.    I.     Goven.   Hosp.  Washington,   1909. 

."^zecsi  S. :  I'.eitrage  zu  der  zytoloRischen  Untersuchuni;  der  Lum- 
lirdtliissigkeit.  Monatschr.  f.   I'sychiat.  u.  Xeurol.  1911.  XXIX,  p.  76. 

W'j'.terhoiise  k  :  Cysticercus  cellulosae  in  the  central  nervous 
s'.:-teni.     Ouart.  Med.  Jour.,   1913,  \'I,  p.  4''>')- 


H 


CHAPTER  XI 

VVASSERMANX  REACTION 

The  tlicory  on  which  the  Wasscrmann  reaction  was  origin- 
ally based,  namely,  the  Ronlet-CcnKou  phenomenon,  is  com- 
parativelv  simple.  When  an  antij^en.  such  as  a  microiirRan- 
ism  or  red  blood  cell,  is  l)ron,^;ht  into  contact  w'th  its  cor- 
responding antibody  in  the  presence  of  complement,  union 
between  these  three  substances  takes  place,  and  the  complement 
is  no  longer  free  to  enter  into  another  combination. 

Five  substances  are  used  in  the  test :— Complement  and  two 
sets  of  antigen  and  antibody.  The  antibody  is  commonly  re- 
ferred to  as  amboceptor.  The  first  antigen-amboccptor  com- 
plex may  be  called  the  reacting  set.  for  to  it  the  complement 
is  added  with  the  object  of  testing  whether  union  of  the 
three  will  occur.  Should  any  of  the  three  be  absent  no  re- 
action will  take  place,  and  the  complement  will  be  free  to 
enter  into  another  combination.  Of  these  three  bodies  in 
the  test  tul)e  only  one  is  unknown.  The  syphilitic  antigen 
and  the  complement  are  supplied  in  every  case,  but  the  pa- 
tient's serum  may  or  may  not  contain  the  syphilitic  ambo- 
ceptor. If  it  does,  union  will  occur,  and  complement  will  be 
bound.     If  it  does  not,  compleirient  will  remain  free. 

In  either  case,  however,  no  outward  or  visiljle  sign  will 
have  occurred  in  the  clear  fluid  in  the  test  tube.  An  indi- 
cator must  therefore  be  added.  The  second  antigen-ambo- 
ceptor  set  may  be  called  the  indicator  set,  for  by  means  of 
it  we  may  readily  determine  whether  complement  has  l)een 
bound  or  still  remains  free  in  the  tube. 

The  indicator  antigen  consists  of  the  red  blood  cells  of  a 
sheep.  The  indicator  amboceptor  is  the  blood  serum  of  a 
rabbit,  which  has  been  sensitized  against  the  sheep's  red  cells 

73 


74     I'livsioi.iM.v   \M>  i-AiMoiocN  or  nii:  cnRiiiRosi-is  \i.  fluid 


In-  rcjK'ati'd  inject  inn.  As  loiij;  as  tluTo  is  n.>  ciiiplcinnit 
ill  the  iiiiliiator  set,  'u>  \\.:mi>\\-\^  will  (Cdir,  Iml  wlicii  nmi- 
plc'HU'iit  i^  ailik'd  in  ciirrert  proiinrlicm  union  ami  Ii.vtni)Iysis 
will  readily  take  place,  in  the  indicator  we  have,  then,  a 
ready  means  of  detenninin-,'  the  presence  or  ali-.ence  of  free 
complement,  .and  thus  t!ie  prc-ence  or  .aloence  of  the  syphilitic 
aml»ocei)lor  in  the  patient's  ^crum. 

In  short,  the  conipUnient  's  tirst  i^i\en  tlie  oiiportnnity  of 
cotnhinin.i;  with  the  reactinij  set.  It  is  then  offered  the  in- 
dicator, 'llie  result  of  this  second  offer  i-  shown  hy  the 
pre-eiice  or  .ahsence  tif  h:inioly-.i>. 

It  is  now  known  that  the  reacliou  is  mt  ;i  -iKH-ific  one  for 
the  spiroch.-ita  pallida,  hut  is  r.ither  ;ui  indication  that  the 
serum  exaniine'I  pos^cs-e^  the  pro]ierty  of  enterin-;  into  a  firm 
comliinatio.n  willi  coinplcmenl  in  the  pres^'iice  of  cert.ain  suh- 
stances  of  a  liji^d  nature,  which  may  l>e  used  as  an  .-nitii^en. 
.\Ithou!:;h,  however,  tlu-  tl'.eoretical  foundation  has  heen  cut 
away  so  tliat  the  rcaciiou  now  haiiijs,  as  has  lieen  s.iid,  like 
M.ahoniet's  cofiiu  i!i  the  air.  it  has  not  on  that  account  lost 
one  iota  of  its  jiractical  \ahie. 

M;my  modifications  have  heen  introduced  from  time  to  time, 
mostlv  with  tlie  ohject  of  simplifying:  the  technic.  Simplicity, 
however,  may  he  linnf:;ht  too  dearly,  when  the  price  to  he 
paid  is  loss  of  reliahility.  The  Wassermann  reaction  is  at 
])resent  essentially  a  lahoratory  procedure,  and  there  is  as  yet 
no  indication  that  it  is  on  the  high  road  to  hecome  a  method 
for  the  hcdsidc  or  even  for  the  office. 

The  onlv  two  valuahlc  modifications  of  the  ori^^inal  method 
are  the  sni)stitution  of  an  anligen  of  human  heart  reenforced 
with  cholesterin  for  the  oripjinal  syphilitic  liver,  and  the  use 
of  larcrer  riuantitics  of  cerebrospinal  fluid.  Mcintosh  and 
Fildes  in  an  exhaustive  investigation  of  the  subject  in  1013 
showed  that  both  for  neurological  and  cjcncral  work  the  cholos- 
terini<ed  heart  autism  was  sn])erior  to  everv  other,  ami  sub- 
sef|uent  work  has  confirmed  this  estimate.  This  anti.tjen  con- 
sists ()'■  a  mixture  of  3  parts  of  alcoholic  heart  extract  with 
2  parts  of  a  i  per  cent,  alcoholic  solution  of  cholesterin. 


WASSERMANN    REACTION 


7S 


The  Wasscrmann  test  may  l.c  applied  t.i  the  spinal  Ihixl 
as  readily  as  to  the  blood  serum,  hut  certain  differences  m  the 
two  case-,  must  In;  taken  into  consideration.  The  spinal  Hind 
is  tested  for  the  presence  of  syphilitic  amlniceptor.  I  f  such 
is  present  it  is  a  proof  that  syphilitic  infection  of  the  central 
nervous  system  has  occurred.  Sy.stemic  syphilis  not  involvinp 
the  ner\ous  system  produces  no  change  in  the  spinal  fluid. 

When  hlood  serum  is  used  it  is  inactivated  by  heat,  partly 
t,.  destroy  its  complement,  partly  to  remove  non-specific  suIh 
stances,  which  sometimes  give  a  false  inhibition.     TMaut  in 
his  HandlKiok  says  that  the  spinal  fluid  must  also  l>e  heated. 
Mcintosh  and  Fiidcs  came  to  the  conclusion  from  their  work 
on  the  subject  that  the  process  of  inactivation  had  little  if  any 
effect  on  the  specific  reacting  substance,  whether  occurring  in 
the  blood  or  the  fluid.     In  general  paresis  and  tabes  dorsalis 
the  specific  substance  is  the  only  one  present,  and  the  question 
of  inactivation  is  not  therefore  of  great  importance.     In  active 
cases  of  cerebrospinal  syphilis,  however,  other  substances  ap- 
pear in  the  fluid  which  tend  to  make  the  reaction  stronger. 
These  substances  are  thcrmolabile.  and  therefore  disappear 
on  inactivation.     It  is  true  that  the  action  obtained  owing  to 
the  presence  of  these  thcrmolabile  bodies  is  in  a  sense  non- 
specific, but  in  practice  this  non-specificity  may  be  disregarded. 
That  is  to  sav,  an  unheated  fluid  from  a  non-syphilitic  case 
will  never  give  a  positive  Wassermann  reaction,  and  from  the 
practical  point  of  view  that  is  all  the  specificity  that  can  l)e 
desired.     It  is  evident   therefore,  that  the  test  should  always 
be  performed  on  unheated  fluid,  and  it  is  prolnble  that  if  this 
precaution  had  been  observed  there  would  not  have  l>een  the 
large  number  of  negative  results  obtained  by  the  earlier  work- 
ers in  cases  of  cerebrospinal  syphilis. 

The  amount  of  spinal  fluid  to  be  used  is  a  subject  regard- 
ing which  considerable  discussion  has  taken  place.  Mcintosh 
and  Fildes  recommend  that  only  twice  as  much  fluid  as  serum 
should  be  used,  'i  he  largest  amount  of  fluid  which  they  use 
is  0.2  c.c.  In  19.11,  however.  Hauptmann  introduced  his 
"  Auswertungsmethode,"  in  which  increasing  quantities  up  to 


76       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

TO  c.c.  of  fluid  are  used.  Although  this  practice  I  is  heen 
severely  condemned  in  sonic  quarters,  there  can  I>e  no  i|uestion 
that  it  represents  a  jjrcat  advance  in  the  application  of  the 
W'assermann  test  to  the  spinal  lluid.  For  hy  means  of  it  it 
is  now  possible  to  obtain  positive  results  in  the  great  majority 
of  cases  of  cerebrospinal  sypliilis  and  tabes  dorsalis.  and  all 
the  work  which  has  been  done  up  to  the  present  goes  to  prove 
that  with  careful  tcchnic,  including  titration  of  complement 
and  amboceptor,  there  will  be  no  non-specific  results. 

In  my  own  work  I  em])loy  five  tunes  as  much  spinal  fluid  as 
blood  serum.  It  is  very  important,  IiDwever,  ahvavs  to  set  up  a 
control  to  which  no  antigen  has  been  added,  so  that  any  non- 
specific inhibitory  action  of  the  large  amount  of  fluid  mav  l)e 
readily  detected.  The  method  has  its  greatest  use  in  the  esti- 
mation of  the  cfifcct  of  treatment.  .\t  the  conmiencement  of 
treatment  the  reaction  may  be  positive  with  0.05  c.c.  then  with 
0.1  c.c.  and  finally  there  may  be  a  negative  result  with  r.o  c.c. 
In  such  a  case  the  physician  fee  is  that  he  really  has  produced 
some  improvement  in  bi^  ])atient.  In  many  cases  of  neuro- 
syphilis it  will  be  found  that  no  reaction  is  obtained  with  o.  i  c.c. 
or  0.2  c.c,  but  a  well  marked  reaction  with  i.o  c.c.  In  studying 
statistics  of  results  it  is  very  necessary,  therefore,  to  know 
what  quantity  of  fluid  has  been  useil.  The  large  quantities 
are  not  of  value  in  differentiating  between  different  varieties 
of  neurosyphilis,  as  between  cerebrospinal  syphilis  and  paresis. 
For  such  a  purpose,  only  o. i  or  0.2  c.c.  should  be  employed. 
In  even*  case,  then,  r.o  c.c.  «if  fluid  should  be  used,  but  also 
decreasing  quantities  down  to  0.03  or  0.25  c.c.  Only  in  this 
way  can  a  true  and  just  estimate  of  the  condition  of  the  fluid 
be  obtained. 


THE  RESULTS  OF  THE  REACTION 

Although  the  theoretical  basis  for  the  specificity  of  the 
reaction  can  no  longer  be  maintained,  each  year  sees  the 
practical  value  of  the  test  more  thoroughly  established.  In 
the  case  of  the  serum  there  are  certain  conditions  in  which 
there  may  be  ambiguity.     The  only  conditions,  however,  in 


WASSERMANN    REACTIOK 


77 


which  a  positive  reaction  has  ever  been  found  in  a  non- 
syphilitic  spinal  fluid  are  leprosy  and  sleeping  sickness,  neither 
of  which  need  be  considered  from  the  standpoint  of  ordinary 
practice. 

The  results  of  the  test  in  the  various   forms  of  neuro- 
syphilis will  Ix;  discussed  in  a  later  chapter.     A  few  general 
conclusions  may,  however,  be  stated.     The  reaction  is  ex- 
tremely c(jnstant  and   very   intense  in  the  blood  and  spinal 
tluid  in  paresis.     Xo  other  condition  gives  so  strong  a  re- 
action in  the  iluid.      It  is  jjositivc  in  at  least  96  per  cent,  of 
cases.     Very  rarely  there  may  be  a  positive  reaction  in  the 
iluid,  but  not  in  the  blood,  or  vice  versa.     Tabes  gives  a  lower 
proportion  of  positive  results.     With  0.2  c.c.  of  fluid  not  more 
than  Co  per  cent,  will  lie  found  positive,  although  a  few  work- 
ers,   .such    as    Mcintosh    and    Fildes,    report   higher    figures. 
When  i.o  c.c.  of  fluid  is  used  the  results  will  nearly  approach 
those  of  paresis,  especially  when  both  the  blood  and  the  spinal 
fluid  are  taken  into  consideration.     For  in  tal>es  it  is  not  at 
all    .ncomnion  to  find  that  the  blood  alone  or  the  fluid  alone 
gives  a  positive  reaction.     In  a   suspected   case,    therefore, 
a  negative  result  in  the  blood  should  always  be  followed  by 
an  examination  of   the  spinal  fluid.     Cerebrospinal   syphilis 
generally  gives  a  positive  reaction  in  the  blood,  but  often  a 
negative  one  in  the  fluid.     Here  again,  however,  the  reaction 
will  be  more  constant  if  the  larger  amounts  of  fluid  are  used. 
With  0.2  c.c.  only  about  30  per  cent,  of  the  cases  are  positive. 
Finally,  cases  of  syphilis  which  show  no  evidence  of  involve- 
ment of  the  central  nervous  system  may  give  a  positive  re- 
action in  the  spinal  fluid  if  i.o  or  even  2.0  c.c.  be  used.     In 
such  cases  the  smaller  quantities  will  always  give  a  negative 
result.     Although  in  these  cases  there  is  no  clinical  evidence 
of  a  syphilitic  infection  of  the  nervous  system,  pathological 
evidence  is  supplied  by  the  presence  of  cellular  and  protein 
changes  in  the  spinal  fluid,  and  the  characteristic  histological 
lesions  will  be  found  at  autopsy. 


\W 


id 


i 


78       PHYSIOLOGY  AKD  PATHOLOGY  OF  THE  CEREBROSPIMAL  FLUID 


Ki:i'i:Ri:\tKS 

Ilaiiptinaiiii  A.:  Die  \oiteilc  dcr  V'ciwcnJung  grosscrer  Liquor- 
nicngeii  ("  Auswertungsmclliodc ")  bci  dor  W'asscrinaiinscheii 
Keaktion  fiir  die  neurologische  Diai;nostik.  Deutsche.  Ztschr.  f. 
Xcrvcnh.     191 1,  XLII,  p.  240. 

Mcintosh  J.  and  Fildes  P.:  The  Wasscrniann  reaction  in  its  ap- 
plication to  neurology.     Lirain,   1913,  XXXVI,  p.  193. 


CHAPTER  XII 
THE  COLLOIDAL  GOLD  REACTIOX  OF  LAXGE 

The  colloidal  gold  reaction  was  primarily  intended  to  show 
variations  in  the  protein  content  of  the  cerebrospinal  fluid, 
but  it  is  considered  apart  from  the  other  reactions  for  protein, 
partly  lx;cause  of  the  peculiar  nature  of  the  reaction,  the  exact 
mechanism  of  which  is  still  undetermined,  and  partly  because 
of  the  very  special  nature  of  the  technic. 

The  reaction  arose  out  of  the  researches  of  Zsigmondy, 
who  in  looi  discovered  that  solutions  of  proteins  protect  col- 
loidal solutions  of  gold  and  other  metals  from  being  pre- 
cipitated by  electrolytes,  the  degree  of  protection  being  cap- 
able of  being  expressed  numerically.  Lange  in  1912  at- 
tempted to  apply  this  method  to  the  cerebrospinal  fluid  in  order 
to  determine  the  amount  of  protein  present.  He  found,  how- 
ever, that  the  protein  not  only  did  not  protect  the  colloid,  but 
actually  facilitated  its  precipitation.  Using  a  series  of  dilu- 
tions of  spinal  fluid  containing  an  increased  amount  of  pro- 
tein he  obtained  a  maximum  reaction  sometimes  with  one  di- 
lution, sometimes  with  anotlicr.  The  cases  giving  a  maximum 
reaction  with  one  dilution  were  found  to  fall  into  one  clinical 
class,  while  those  which  gave  a  maximum  reaction  with  an- 
other dilution  fell  into  another  clinical  class.  The  reaction  was 
not  dependent  on  the  rjuantity  of  protein  present. 

Thus  the  reaction  is  of  value  for  dififercntiating  one  patho- 
logical condition  from  another,  rather  than,  as  was  first  ex- 
pected, for  making  a  quantitative  determination  of  the  pro- 
tein. 

The  technic  is  one  which  demands  a  considerable  amotmt 
of  care,  the  chief  diflleulty  being  the  preparation  nf  the  rn]- 

79 


8o       PHYSIOLOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


it 


■'I 

i'i 


loidal  gold  solution.  This,  however,  can  he  overcome  if  the 
requisite  precautions  are  taken  in  handlinp;  the  glassware  and 
in  preparing  the  distilled  water. 

Preparation  of  the  Colloidal  Gold  Solution. —  In  a  liter 
flask  is  placed  500  c.c.  of  fresh  doubly  distilled  water.  The 
flasks,  of  the  best  Jena  glass,  must  he  thoroughly  washed  out 
with  strong  H  CI,  followed  hy  distilled  water,  and  sterilized  by 
hot  air  for  half  an  hour.  All  glassware  used  should  l)e  treated 
in  the  same  manner.  The  distilled  water  must  be  prepared  in 
a  sterile  all-glass  condenser,  and  must  not  be  allowed  to  come 
in  contact  with  any  rubber  connections,  nor  allowed  to  stand 
more  than  a  couple  of  hours.  The  preparation  of  the  di.stilled 
water  is  the  most  important  part  of  the  tcchnic,  and  unless  the 
alxjve  precautions  be  taken  a  satisfactory  solution  will  not  be 
obtained. 

The  water  is  heated  to  60"  C.  and  5  c.c.  of  a  2  per  cent, 
solution  of  potassium  carbonate  are  added,  followed  immedi- 
ately by  5  c.c.  of  a  i  per  cent,  solution  of  gold  chloride.  The 
solution  is  now  rapidly  heated  with  the  aid  of  several  Bunsen 
burners,  and  the  moment  the  first  bubbles  a]ipcar  the  flame  is 
removed,  and  5  c.c.  of  a  i  per  cent,  solution  of  formalin  are 
added,  the  contents  of  the  flask  being  rapidly  rotated. 

The  gold  is  at  once  reduced  to  a  colloidal  state,  and  the 
colorless  fluid  changes  t(^  a  dt-cp  cherrv  red.  Ihe  fluid  should 
be  absolutely  clear  and  transparent.  The  appearance  of  the 
slightest  translucency  or  fluorescence  indicates  some  fault  in 
the  preparatiiMi.  After  the  fluid  has  stood  for  a  few  days 
there  should  be  no  bluish  deposit  on  the  sides  of  the  flask. 
Finally  the  solution  should  Ik?  tested  against  the  spinal  fluid 
of  a  known  general  paretic,  and  ought  to  give  the  typical 
reaction  in  the  "  paretic  zone."  that  is  to  say  complete  .his- 
Hockiiuf/.  in  the  first  4  or  5  tubes. 

Technic  of  the  Test. —  A  series  of  10  test  tubes  is  set  up. 
Tn  the  first  tube  ])lace  1.8  c.c.  of  0.4  jier  icnt.  salt  solution. 
It  is  well  to  prepare  this  dilution  freshly  fron.  a  stock  in  per 
cent,  .solution.     In  each  of  the  other  tubes  place  i  c.c.  of  the 


THE   COLLOIDAL   GOLD   REACTION   OF   LANCE 


8i 


salt  solution.  To  the  first  tube  is  added  0.2  c.c.  of  spinal 
fluid,  and  thoroughly  mixed,  a  i  in  10  dilution  being  thus  ob- 
tained. Transfer  i  c.c.  of  fluid  from  the  first  to  the  second 
tube,  thus  getting  a  dilution  of  i  in  20.  This  procedure  is 
repeated  for  each  tube  till  a  series  of  10  dilutions  is  obtained, 
ranginr  from  i  in  10  to  i  in  5120.  To  each  tube  is  now 
added  5  v.c.  of  colloidal  gold,  and  mixed  with  the  fluid  as 
rapidly  as  possiI)le.  The  test  may  l)e  read  after  5  minutes, 
but  it  is  l)etter  to  allow  the  tulles  to  stand  at  room  temperature 
12.  hours. 

The  result  is  expressed  in  lig-ircs  or  in  the  form  of  a  curve, 
not  merely  as  positive  or  negative,  'ihe  red  color  may  remain 
unchanged,  or  tliere  may  be  complete  decolorization  due  to 
complete  precipitation  of  the  colloidal  gold.  Between  these 
two  extremes  there  may  be  varying  grades  of  bhie  and  red 
to  which  a  numerical  value  is  attached  as  follows : 


Colorless    5 

Blue    4 

Violet    3 

Red  blue    2 

Slight  change  in  the  red i 

Red  o 

The  color  change,  if  any,  may  be  most  marked  in  the  lower 
dilutions,  in  the  middle  dilutions,  or  in  the  higher  dilutions. 
The  position  of  the  maximum  change  in  the  series  of  dilutions 
is  of  equal  importance  with  the  color  change  itself,  and  for 
this  reason  the  result  is  best  represented  by  a  curve,  or  it  may 
be  expressed  as  a  series  of  10  numljers  in  which  the  degree  of 
change  is  represented  by  the  numbers  o  to  3.  Thus  if  no 
change  occurred  in  any  tube  the  result  would  be  0000000000, 
whereas  if  complete  reduction  occurred  in  the  first  3  tubes  but 
no  change  in  the  remaining  ones  it  would  be  5550000000. 

If  expressed  graphically  the  following  curves  would  Ije  ob- 
tained : 


82       PHYSIOIOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


1 

2       3       ^ 

5 

6 

7 

8 

9 

10 

5 

4 
3 
2 

1 
0 

* 

* 

I.     Colloidal  KoUl  curve.     \o  rcilitction. 


1 


w 


\ 

2 

3 

4 

5 

6 

7 

8 

9 

10 

5 
4 
3 
2 
1 
0 

* 

\ 

v 

* 

' 

' 

2.    Colloidal  gold  curve.    Reduction  in  first  three  tubes. 

Two  reactions  occurring  with  sufficient  frecjuency  to  merit 
the  term  characteristic  have  so  far  been  found,  the  meningitic 
zone  reaction  and  tlic  paretic  zone  reaction. 

In  a  typical  meningitic  reaction  no  change  occurs  with  the 
low  dilutions,  but  in  the  higher  dilutions  there  may  be  marked 
precipitation.  This  phenomenon  has  Ix-en  termed  by  Lange 
"  Verschiebung  nach  oben."  and  is  illustrated  by  the  following 
curve : — 


i       23456789      10 

5 
4 
3 
2 

I 
0 

. 

/ 

\ 

/ 

\ 

/ 

\ 

I 

/ 

\ 

/ 

V 

/ 

\ 

3.    Colloidal  gold  curve.    Acute  tneningitis. 


THE  COLLOIDAL  COLD  REACTION  OF  LANCE 


83 


The  paretic  curve  occurring  in  general  paresis  is  the  most 
important  and  characteristic  of  the  reactions.  There  is  com- 
plete precipitation  in  the  paretic  zone,  namely  the  first  3,  4  or 
5  tuljes,  followed  by  an  abrupt  drop  to  xero.  The  following 
is  a  typical  example :  — 


1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

5 
4 
3 
2 

1 
0 

* 

* 

* 

\ 

> 

\ 

\ 

\ 

\ 

k 

\ 

~* 

4.    Colloidal  gold  curve.    General  paresis. 

In  talies  dorsalis  and  cerebrospinal  syphilis  if  a  reaction 
occurs  at  all  it  does  so  in  the  mid-zone,  is  moderate 
in  degree,  and  is  readily  distinguished  from  that  of  general 
paresis.  It  may  be  that  further  work  will  make  modification 
of  these  statements  necessary,  but  at  present  there  is  every 
reason  to  believe  that  the  colloidal  gold  test  is  a  valuable  means 
for  differentiating  general  paresis  from  other  syphilitic  af- 
fections of  the  nervous  system.  In  these  other  conditions  the 
curve  in  the  mid-zone  has  been  considered  sufficiently  char- 
acteristic to  earn  the  title  "  luetic  curve."  Grulee  and  Moody 
found  a  similar  result  in  a  series  of  cases  of  congenital  syphilis. 

It  may  thus  I)e  said  that,  speaking  generally,  a  marked  re- 
action in  the  first  zone  is  extremely  characteristic  of  general 
paresis;  one  in  the  mid-zone  suggests  nervous  syphilis,  and 
one  in  the  end  zon*^  acute  meningitis.  Of  these  the  least 
reliable  are  the  mid-zone  results. 

The  curve  in  general  paresis  corresponds  closely  with  the 
positive  Wassermann  reaction  in  that  condition,  but  that  the 
two  reactions  are  not  dependent  on  the  same  substance  has 
been  demonstrated  by  Weston. 


84       PHVSIOLOCV  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


1 


r 

h 


THE  MASTIC  TEST 

The  colloidal  gold  test,  although  exquisitely  sensitive,  is 
undoubtedly  a  diflicult  one  to  carry  out  in  practice.  The  gold 
chloride  solution  may  be  prepared  five  times,  using  exactly  the 
same  technic  on  each  occasion  with  eminently  satisfactory 
results,  and  yet  the  sixth  attempt,  carried  out  in  precisely  the 
same  way,  may  result  in  complete  failure. 

On  account  of  this  difticulty  several  attempts  have  been 
made  to  employ  other  colloids  which  would  be  simpler  to  pre- 
pare. Of  these  the  emulsion  of  mastic  introduced  by  Emanuel 
for  the  purpose  has  proved  the  most  succesful.  At  first  the 
emulsion  was  too  sensitive,  for  precipitation  took  place  when 
it  was  mixed  with  salt  solution,  apart  from  the  presence  of  a 
pathological  spinal  fluid.  Cutting  has  suggested  the  addition 
of  a  very  dilute  solution  of  potassium  carbonate  to  the  saline, 
and  certainly  this  prevents  any  precipitation  of  mastic  except 
in  the  presence  of  a  pathological  spinal  i1uid.  The  test  is  still 
in  its  infancy,  but  controls  made  with  the  colloidal  gold  method 
lead  us  to  believe  that  in  the  mastic  test  we  have  a  simple 
and  valuable  method  for  estimating  the  effect  of  pathological 
spinal  fluids  upon  colloidal  solutions. 

The  test  is  conveniently  performed  as  follows:  A  stock 
solution  of  lo  gm.  of  gum  mastic  in  lOO  c.c.  of  absolute 
alcohol  is  made  up,  and  may  be  kept  indefinitel).  Of  this  stock 
solution  2  c.c.  is  diluted  with  8  c.c.  of  absolute  alcohol  and 
mixed  rapidly  with  8o  c.c.  of  distilled  water.  To  99  c.c.  of 
a  1.25  per  cent,  solution  of  sodium  chloride  in  distilled  water 
is  added  i  c.c.  of  a  0.5  per  cent,  solution  of  potassium  car- 
bonate in  distilled  water. 

In  a  series  of  6  small  test  tubes  place  the  combined  salt  and 
carbonate  solution.  1.5  c.c.  in  the  first  tul)e,  and  i  c.c.  in  the 
other  tubes.  To  the  first  tube  is  added  o.5  c.c.  of  cerebrospinal 
fluid,  and  then  1  c.c.  is  transferred  from  each  tube  to  the  next 
in  the  series  in  the  usual  way.  the  last  cubic  centimeter  being 
thrown  away,      lo  each  tube   i  c.c.  of  the  prepared  mastic 


f^ 


n  i'^  s 


n::    iiiii 


THE  COLLOIDAL  COLD  REACTION  OF  LANCE         15 

solution  is  addctl  and  well  stirred,  the  tuljcs  are  incubated,  and 
read  next  morning.     (Fig.  5.) 

In  positive  cases  a  complete  precipitation  of  the  mastic  oc- 
ctirs  in  a  given  numlier  of  tubes,  and  the  results  are  read  in 
the  same  way  as  in  the  colloidal  gold  test.  When  precipitation 
is  complete  the  fluid  I)ecomcs  perfectly  clear,  and  there  is  a 
heavy  white  deposit  at  the  bottom  of  the  tube. 


REFERENCES 

Cuttinp,  J.  A.:  A  new  m.ist!c  test  for  the  .spinal  fluid.  Jour. 
Am.  Med.  Assoc,  1917,  LXVIII,  p.  1810. 

Emanuel,  G. :  Fine  ncue  Reaktion  zur  Untersuchung  des 
Liquor  cerebrospinalis.     Berl.   klin.   Wchnschr.,    1915,  LII.   p.  781. 

Grulee,  C.  G.  and  Moody.  A.  M.:  Tlic  Lange  Rold  chloride  re- 
action on  the  cerebrospinal  fluid  of  infants  and  young  children. 
Am.  Jour.  Dis.  Child.,  1915,  IX,  p.  17. 

Lange,  C. :  Die  Ausflockung  Kolloidalen  Goldcs  durch  Cercbro- 
spinalfliissigkeit  bei  syphilitischen  Aflfectionen  des  Ccntralnerven- 
systcms.    Ztschr.  f.  Chemotherapic,  1912,  No.  I. 

Miller,  S.  R.  and  Levy,  R.  L. :  The  colloidal  gold  reaction  in  the 
cerebrospinal  fluid.     Bull.  Johns  Hopkins  Hosp.,  1914,  XXV,  p.  133. 

Weston,  Paul  G. :    The  colloidal  gold  precipitating  substance  in 
the  cerebrospinal  fluid  in  paresis.    Jour.  Med.  Res.,  1916,  XXXI 
p.  107. 

Zsigmondy:    Ztschr.  f.  anal.  Chem.,  1901,  XL,  p.  697. 


■f 


V. 


CHAPTER  XIII 
BACTKUlOLUCilCAL  M  in  HODS 

It  is  by  no  means  necessary  to  make  a  bacteriolog  cal  exami- 
nation i)f  every  spinal  lluid  witi-.drawn.  Wlicre,  liowcver,  it 
is  intended  to  make  such  an  examination  —  in  cases  where 
an  acute  liacterial  infection  of  the  meninges  is  suspected  — 
special  precautions  must  l)e  observed  in  witlidrawiufj  the  fluid. 
'Ilie  needle  and  skin  must,  of  course,  l)e  very  thoroughly 
sterilized.  The  fluid  should  be  collected  in  at  least  tt\x)  sterile 
tubes. 

Special  care  should  Ije  excicised  'o  prevent  contaminalion 
of  the  fluid  at  the  point  where  it  issues  from  the  needle.  It 
is  best  if  possible  to  have  a  special  needle  carrying  a  stout 
stilette  with  an  expanded  extremity  which  is  grasped  by  the 
hand  when  the  puncture  is  l)cing  made,  and  is  subsequently 
withdrawn.  By  this  means  the  fingers  do  not  come  in  c<mi- 
tact  with  the  point  at  which  the  fluid  issues.  Even  more  con- 
venient is  the  form  of  needle  in  which  there  is  a  solid  handle 
from  which  the  continuation  of  the  hollow  part  branches  ofT  in 
a  gentle  curve.  If  neither  of  these  forms  are  available,  the 
needle  may  be  held  in  a  piece  of  sterile  gauze,  and  the  flrst 
few  drops  of  fluid  allowed  to  escape  before  the  collection  is 
bcgtm. 

The  fluid  in  one  tube  is  centrifuged,  and  films  made  from 
the  centrifugcd  deposit.  If  the  fluid  is  at  all  purulent  centri- 
fuging  will  not  be  necessary.  The  films  are  stained  with 
methylene  blue  and  examined  for  inicro(')rganisnis.  In  tuber- 
culous meningitis  a  delicate  skein  usually  forms  which  bangs 
down  from  the  surface  of  the  flui^!  provided  that  the  latter  is 
not  agitated.  The  best  method  of  detecting  the  tubercle 
bacillus  is  tn  spread  this  skein  nut  on  a  slide  and  stain  it  bv 

the  Ziehl-Neelson  method. 

86 


BACTERIOLOCICAL   METHODS 


•7 


In  streptococcal  and  pneumococcal  menin^tis  the  infecting 
organism  will  usually  be  found  in  the  direct  smears.  In  men- 
ingococcal cases,  however,  none  may  be  dett  :ted  even  after 
prolonged  search,  but  if  the  tUiid  l)e  placetl  in  the  incubator 
over  night  considerable  nunil)crs  of  meningococci  may  make 
their  apiKjarance.  This  device  will  also  be  found  to  give  a 
larger  nuiulxT  of  ix)>itive  cultures  from  (luids  in  which  the 
organisms  are  present  in  very  small  numljers. 

The  second  specimen  of  lluid  is  to  l)e  used  for  cultural 
purposes.  Cultures  may  l)e  made  on  blood  senim  or  ordinary 
agar,  but  the  JK-'st  ali-rouiid  medium  is  undoubtedly  blood  agar, 
recommended  by  Schottniiiiler,  on  which  any  of  the  organism.s 
of  meningitis  will  grow  readily  and  in  characteristic  fashion. 
The  tubes  or  plates  should  be  incubated  for  at  least  48  hours 
K-fore  a  negative  result  is  reported.  Hlood  agar  will  be  found 
especially  useful  when  dealing  with  such  a  condition  as  in- 
fluenzal meningitis.  In  doulrtful  cases  of  tuberculous  men- 
ingitis in  which  no  1...  '■  can  be  detected  in  the  smears  a 
guinea  pig  should  be  inc  .lated  with  the  centrifuged  deposit. 
The  time  re(|uired  for  signs  of  tulrrculosis  to  manifest  them- 
selves in  the  animal  may  be  shortened  by  first  exposing  it  to 
the  X-ravs. 


REFERENCE 

Plant,  Rchni.  and  Schottmuller :    Leitfaden  zur  Untersuchung  der 
Ccrcbrospinalflussigkeit,  1913,  Fischer,  Jena. 


u  ■ 


ir 


I! 


::' 


PART  II 
SPECIAL 


f:l 


CHAPTER  XIV 
MEXIXGITIS 

The  sul)arachnoid  space  is  so  thorou<Thly  slnit  off  from  the 
general  circulation,  and  so  efficiently  sU'irded  fro'n  injurious 
agents  which  may  he  circulating  in  the  hlood,  tint  haniato- 
genous  infection  of  the  meninges  is  comparatively  uncommon. 
In  the  inniediate  vicinity,  however,  are  such  cavities  as  the 
naso-pharynx,  the  sinuses  of  the  nose  and  skull,  and  the  mid- 
dle ear,  c  ities  either  septic  in  themselves,  or  very  liahle  to 
become  so.  Infection  may  spread  from  these  areas  to  the 
meninges,  all  the  more  readily  hccause  of  the  various  nerves 
passing  from  the  inside  to  the  outside  of  the  cranial  cavity, 
nerves  which  are  accompanied  by  lymphatic  vessels  which 
form  a  natural  route  for  an  ascending  infection. 

The  examination  of  the  cerebrospinal  fluid  has  thrown  li^ht 
upon  many  obscure  conditions  in  clinical  medicine,  but  it  is 
in  acute  meningitis  that  it  has  proved  of  the  greatest  value, 
Ixith  as  regards  diagnosis  and  treatment.  For  no  diagnosis 
of  meningitis  can  be  accepted  nowadays  unless  the  cerebro- 
spinal fluid  has  been  examined,  and  many  an  obscure  case  has 
onlv  been  shown  to  be  really  one  of  meningitis  when  a  lumbar 
puncture  has  been  done. 

Almost  every  known  i)athogenic  nu"cro(")rganism  has  been 
described  as  occurring  in  meningitis,  but  only  four  are  found 
with  any  degree  of  frequency.  These  are  the  meningococcus, 
the  pneumococcus,  and  the  tulx;rcle  bacillus. 

Although  the  vast  majority  of  cases  of  meningitis  are  or- 
ganismal  in  origin,  it  must  be  remembered  that  acute  inflam- 
mation of  the  meninges  may  be  due  to  a  non-bacterial  irritant. 
Thus  Purves  Stewart  produced  an  inflammatory  reaction  ac- 
companied by  characteristic  polynuclear  leucocytosis  in   the 

9J 


I  I 

r: 


.| 


92      I'livsiouKiv  AM)  p.atm()i..k;v  oi   Till;  ci;rebr()si.inal  fluid 

fluid  in  tlic  simple  injection  ,.|  Merilc  suit  sointion  or  a  sterile 
crmilsion   of   colored   particles    into   tlie   suharachnoid    space. 
This  IS  a  fact  of  considcrahle  importance  in  these  davs  when 
all  sorts  and  con.litions  of  substances  are  hein-  iniected  into 
the  spmal  canal.     That  the  irritative  effects  i.f  .such   injec- 
tions m.iy  he  hv  no  means  iie.di-iMe  is  shown  l.v  the  ohserva- 
tions  of  IiiRleton  on  the  results  produced  hv  the  intrathecal 
uuection  of  antiletanic  serum.     Tlie  spinal  llu'id  was  examined 
helore  injccti,,n  of  the  .<enim  and  a-ain  J  hnurs  later.      In 
every  case  a  well  marked  cellular  reacti(ni  was  ohserved.  the 
cells  aven,-in-  _|,m,  per  c.mm.  with  ,,ver  ()5  ,,er  cent,  of  polv- 
niorphs.      Ill   ,,ne   ca.^e  a.  m:Miy  :is    ir,,,,,   cells   were  presen't. 
I  he  tluul  was  alway>  f,.iind  t,,  he  sterile.      .Ml  ca.ses  conn-n-  to 
autopsy  showe.l  a  (kUni-e  aseptic  menin.i,Mtis  of  varyin-  de- 


S:rees  of  inten^itv 


MENINGOCOCCAL  MENINGITIS 


; 


I  he  dii.l.,coccu.  intncelhilari.  menin-Mtirlis  of  Weichsel- 
haum  ,s  tlie  uv^i  cnnun,.„  invader  of  the  suhanichnoid  .p,ce 
In  appearance  it  clo.cly  reM.nhle..  the  -onococcus.  hut  can  he 
di.stm.^Mushed  from  th.u  or.-ani>m  hv  its  cultural  character- 
istics an<I  hy  a-.;lntiu,-iti,,n  .-ui,!  complement  fixati.m  tests  It 
occurs  m  pairs,  the  ..pp.^.ins  surfaces  usuallv  heimj  somewhat 
flattened.  Occa^-ionrdly  it  is  seen  in  the  f.,rm  of  tetrads  It  is 
negative  to  Cram's  stain. 

_    fn  the  .pinal  llnid  the  nr^ani,-;m  is  mainlv  intracellular    he- 
ui,ir    found   wuhin   the   |)olymorphonncle-ir  Icuco  vtcs,   hut   it 
al-o  occurs   free  in  the  flttid.     The  n.ere   fact  that  the  cocci 
have  hcen  m-ested  hy  leucocytes  does  n.:t  prove  that  the  or- 
pranisms  are  heins  di.c^cstcd  and  are  no  lon-er  viahle.  for  it 
has   heen    >hown    that    livin-   ovrms   m.iv   he   renivererl    from 
such  leucocytes.      It  has  been  su--este<!   that   loucorvtes  mav 
HI  this  wav  act  as  carriers  of  infection  from  the  nose  to  the 
central    nerv.,us    system.     The    numhers    varv    -reatlv      The 
leucocyte,  may  he  cmuded  with  cncci.  presenting  the  appear- 
ance seen  m  a  Him  of  -onor-h-eal  pus.     On  the  other  hand  a 
pro]un^:,rcd  search  may  be  necessary  before  a  sin-le  pair  can 


1 


Meningococcal  Meningitis. 


MnNMXC.ITIS 


93 


l)e  discovered.  A  case  of  nicninjjitis  uitli  purulent  fluid  in 
wlii'.-li  no  ()r,q;niisnis  can  lie  fnund  is  prohalily  one  of  men- 
ingococcal infection. 

Altliougli  hy  no  means  a  universal  rule  it  will  generally  he 
found  that  the  nuniher  of  organisms  hears  some  relation  to 
the  severity  of  the  infection.  In  mild  cases  and  in  the  chronic 
post-hasic  type  the  numhers  may  he  extremely  small.  .\s  im- 
provement sets  in  the  meningococci  dimi"ii>h  in  num1)er>,  he- 
coming  more  and  more  intracellular,  and  finally  disappearing 
altogether.  It  must  be  remembered,  however,  that  the  find- 
ings in  the  fluid  withdrawn  by  lumbar  puncture  may  not  always 
afford  a  true  indication  of  tl'.e  pathological  changes  present, 
(/arnegie  Dickson  has  reported  cases  in  which  the  organisms 
gradually  (lisa])pcarc(l  from  the  spinal  lluii'  without  any  cor- 
responding improvement  on  the  part  of  the  i)atient.  'I'hc  ex- 
planation was  afforded  by  post-mortem  examination,  where  it 
was  found  that  the  communication  between  the  ventricles  and 
the  subarachnoid  space  had  been  cut  off.  The  fluid  in  the 
ventricles  was  extremely  purulent,  and  contained  meningococci 
in  such  numbers  as  to  suggest  the  appearance  of  a  culture  of 
th^  organism. 

On  the  other  hand  the  presence  of  meningococci  in  the 
cerebrospinal  fluid  is  not  an  incontestable  proof  that  a  condi- 
tion of  meningitis  is  present.  For  meningococcal  meningitis 
is  merely  one  aspect  of  the  more  general  condition  cerebro- 
spinal fever,  and  the  septicemia  may  be  so  acute  that  the  pa- 
tjait  dies  Ix^fore  meningitic  changes  have  had  time  to  occur. 
.As  Ilorder  points  out,  "it  is  the  cytology  and  the  chemistry 
of  the  fluid,  rather  than  its  bacterial  content,  which  determine 
the  question  whether  or  no  meningitis  is  present.'' 

Every  effort  to  demonstrate  the  meningococcus  in  smears 
from  the  fluid  should  always  be  made,  for  in  no  condition  is 
successful  treatment  so  dependent  on  early  diagnosis.  When 
these  efforts  are  unsuccessful,  however,  cultures  are  to  be  uiade 
on  suitable  media.  Such  media  should  contain  some  animal 
protein,  since  primary  cultures  do  not  readily  grow^  on  the 
ordinarv  laboratorv  media.     One  of  the  most  suitable  media 


r 
•  i| 


04       PIIVSIOLOGY  AND   PATIIOLOCY  OF  THE  CEREBROSPINAL  FLUID 


Vi     • 


•I 


r 


for  ,i,aMicral  work  is  hlood  .'iRar,  as  rccommciidccl  l)y  Schott- 
iiiiillcr.  .\a>j,Mr  ( inUrosc  ascitic  agar)  lias  been  extensively 
used  l)y  ICiigli^li  workers. 

Tile  orf^'aui-^iii  j^rows  Iiol  at  ,^7  C.  and  growtli  fails  to  take 
place  at  a  temperature  Iielow  _'5  C.  One  of  the  readiest 
methods  of  (li>tiu,t;ui>hiui^  the  meuiuf^ococcus  from  the  other 
Ciraui-nej;at;\e  orj,'auisnis  which  occur  in  conjunction  with  it 
in  tile  nast)-pharynx  is  to  keep  the  cultures  at  room  teni])er- 
ature.  Any  (jram-negative  cocci  which  grow  are  certainly 
not  the  meningococcus. 

-Mthough  the  meningococcus  is  accepted  by  most  authorities 
as  the  sole  and  suffic'ent  cause  of  cerel)rosi)inal  tneningitis,  the 
re-ults  of  some  recent  workers  are  such  that  it  is  still  neces- 
sary to  keep  an  open  mind  on  the  subject,  llort  in  jjarticular 
h.is  recently  published  a  series  of  papers  in  whicli  he  expresses 
the  opinion  that  the  disease  is  cau.sed  by  a  pleomorphic  or- 
.U.inism  of  which  the  meningococcus  is  merely  one  phase,  and 
that  not  the  infectious  pha.se.  The  matter  is  still  too  inde- 
terminate, iiowever,  to  justify  further  discussion  here. 

it  is  at  least  certain  that  different  strains  of  meningococci 
exist.  Agglutination  tests  with  anti.sera  have  deiiuitely 
sei)arated  the  para-meningococcus  of  Dopter  from  the  men- 
ingococcus, and  there  is  already  sufticient  evidence  to  indicate 
that  the  meningococcus  it>elf  can  be  divided  into  3  or  4  types, 
just  as  has  been  done  in  the  case  of  the  pneumococcus. 


« 


Character  of  the  Cerebrospinal  Fluid. —  The  appearance 
of  tie  fluid  varies  with  the  intensity  of  the  infection,  the  stage 
at  which  lumbar  puncture  is  done,  and  with  other  factors  of 
which  we  have  as  yet  imperfect  knowledge. 

The  p  essure  is  almost  invariably  raised,  but  sometimes  not 
to  any  great  extent.  As  high  a  figure  as  650  mm.  of  water 
has  been  recorded.  In  the  chronic  stag'-  communication  with 
the  ventricle  may  become  blocked,  with  a  resulting  low  pres- 
sure of  fluid. 

The  fluid  may  be  opalescent,  cloudy,  or  turliid.  In  the  ear- 
liest stages,  however,  it  may  be  quite  clear,     .\mongst  I'ritish 


MENINGITIS 


95 


soldiers  in  France  I  have  on  more  than  one  occasion  found 
the  fluid  clear  one  day,  hut  (|uite  turbid  on  the  next.  This 
lack  of  turbidity  in  the  early  stages  must  not,  therefore,  bo 
allowed  to  lead  one  astray.  As  convalescence  sets  in  the  fluid 
gradually  clears  up. 

Carnegie  Dickson  has  pointed  out  one  source  of  error  which 
it  is  well  to  bear  in  mind.  In  a  number  of  non-meningococcal 
cases  (tulwrculous  and  syphilitic  meningitis)  anti-meningo- 
coccal  serum  had  been  administered  before  the  case  was  sent 
to  the  hospital.  Lumbar  puncture  subsequent  to  admission 
revealed  a  fluid  identical  with  that  of  meningococcal  mcnini.;i- 
tis  as  regards  turbidity  of  the  fluid,  overwhelming  prepon<ler- 
ance  of  polymorphs,  etc.  When  the  specimen  of  fluid  with- 
drawn before  admission  was  obtained  an  entirely  different 
picture  was  presented.  This  "  serum  reaction  "  is  similar  to 
that  already  described  as  following  the  use  of  anti-tetanic 
serum. 

The  protein  content  of  the  fluid  is  invariably  high.  Cdo- 
bulin  is  greatly  increa.sed  and  albumen  may  be  present  in  con- 
siderable amount.  The  protein  usually  cNcccds  0.3  per  cent, 
and  may  reach  as  high  as  0.8  per  cent. 

The  sugar  is  always  diminished,  and  may  be  nltogothcr  ab- 
sent. The  disappearance  of  the  sugar  is  mainly  due  to  the 
fermentation  action  of  the  meningococcus  upnn  glucose.  T 
have  examined  the  fluid  from  cases  if  cerebrospinal  meningitis 
in  which  there  were  very  few  mcningncocci,  and  wMrli  gave 
a  good  reduction  of  Fchling's  solution.  P>y  incubating  the 
fluid  over  night  the  numl)cr  of  organisms  wa-^  cnorninusly  in- 
creased, and  there  was  a  coincident  disappearance  of  gUico<c 
from  the  fluid.  Manv  authors  niininii;'e  the  importance  of 
examining  for  sugar  in  meningitis.  Tersonallv  T  regard  it 
as  a  useful  bedside  method  which  can  be  carried  out  by  the 
physician  at  the  time  of  tlic  puncture.  W'iii.  a  purulent 
fluid  it  is  of  course  unneccs>arv,  but  in  the  ca'^c  of  a  com- 
paratively clear  flin'd  it  may  well  serve  to  help  to  differentiate 
an  acute  meningitis  from  otlu-r  conditions  simiil.iiiiig  it.  The 
behavior  of  the  sugar  mav  furnish  valuable  information  re- 


96     i-hvsi()i,(m;v  and  iv\tii(h,(k;v  or  Tin;  cirkrrospinai.  fluid 

gardiiif,'  tlic  progress  of  flic  case.  The  sugar  reappears  aliou 
the  fourth  or  liiih  day  in  favorable  cases,  hut  disappear.- 
agaui  if  a  relajj^e  supervenes.  It  is  sometimes  (hflicuh  to  (lis- 
tingui.sh  l)et\veen  a  true  relapse  and  a  reaction  (hie  to  tlie  us< 
of  aiitimeningoeoecal  serum.  In  such  cases  sugar  estimatior 
i.s  of  great  value,  for  in  the  serum  reaction  it  will  show  nc 
aheration. 

Tlic  most  striking  feature  of  the  cerelirospinal  fluid  in  all 
form.s  of  acute  meningitis  is  the  cytological  change  which  is 
invariahly  found.  The  tyi)e  of  cell  depends  on  a  nnmlicr  of 
factors,  -iich  ;is  the  nature  of  t!ie  irritant,  the  intensitv  of  the 
infection,  ;uid  the  stage  of  the  disease.  In  cerelin>s])inal  men- 
ingitis the  iiolymorphonuclear  leuocyte  is  the  preponderating 
cell  in  the  great  majority  of  cases  when  first  seen.  I'rom 
the  few  oliservations  on  record,  however,  it  api)ears  prohahic 
that  the  earliest  cell  to  appear  is  the  lymphocyte,  Iiut  hv  the 
time  that  the  ordinary  case  is  seen  l»y  the  physician  the  fluid 
is  flooded  with  polymorphs,  which  may  con-tilute  (;o  per  cent, 
or  more  of  the  total  cell  count. 

In  a  ca.se  in  which  lumbar  puncture  is  performed  every  day 
for  therapeutic  purposes  it  is  \  cry  instructive  to  watcli  the 
gradual  change  which  comes  over  the  cytological  picture.  In 
a  case  which  is  going  to  recover  the  polymorphs  graduallv 
diminish  in  nmnber.  their  )>lace  being  taken  by  large  mon- 
onuclear phagocytic  cells.  The  jxilyninrphs  lose  their  staining 
power  and  l)ecome  disintegrated,  and  in  the  late  stages  of 
convalescence  the  large  monomiclears  also  stain  faintly,  their 
place  being  taken  by  small  lyiupliocytes.  It  is  said  that  in 
post-basic  meningitis  the  chief  type  of  cell  is  the  small 
lymphocx  te. 

Tn  cases  where  no  org.anism  can  be  found  the  precipito- 
reaction  of  \'incent  and  l!ellot  may  be  tried.  This  is  an  in- 
dication not,  i)ni]ial)l\-.  .'f  .■iniiin  .dies  ],ut  of  autolvsate  of  the 
niening(icnccn>.  |)nidiiccd  by  the  disinte;:rntion  of  the  bodies 
of  the  organisms.  To  a  vmall  (|u:ni!il\-  of  aiilinicnin.gncorcal 
serum  is  added  fmni  io  tn  jo  times  ibc  ,-ininmit  nf  cerebro- 
spinal fltu'd.  which  has  first  been  tliMroughlv  centrifuged.     The 


Pneumococcal  MeniitKitis- 


MF.NINr.ITIS 


97 


fluid  must  l)e  perfectly  fresh.  The  tul)e  is  stoppered  and 
placed  ill  tiie  iiKul)at(>r  ovcrni^^ht.  A  lurltidity  '<r  ..palcM-eiice 
inilicates  a  positive  reaction.  .\  control  consisting;  of  spinal 
tlnid  \viti)out  serum  should  always  he  jmt  uj). 

.Another  test  for  fluid  in  wliich  n.  or^'anisins  can  Ik-  found, 
hut  one  of  whidi  1  have  no  e\perience.  is  that  of  V.  drysez, 
(luoted  hy  ileiman  and  l"e]iKtein.  .\  ,t,'uinea-pin  is  inoculated 
intraspinally  with  0.5  c.c.  of  cerelmxpinal  flui<l.  A  iowerinjj 
of  temperature  of  from  4  to  S  C  occurs  in  a  sliort  time, 
and  death  usually  takes  place  in  from  j  to  -'4  hours  if  the 
case  is  one  of  meningococcal  meningitis. 

PNEUMOCOCCAL  MENINGITIS 

Of  the  ordinary  pyogenic  organi-ms  the  pneumococcus  is 
the  commonest  invader  of  the  cerebral  meninges,  and  pneu- 
mococcal meningitis  ranks  third,  after  the  meningococcal  and 
tuberculous  forms,  in  order  of  frei|uency. 

The  infection  may  be  primary  or  secondary.  In  the  pri- 
mary form  no  other  focus  of  infection  can  l>e  found,  but  the 
meninges,  especially  over  the  vertex,  are  the  seat  of  a  wide- 
spread, yellowish-green,  purulent  exudate  in  wbich  large 
numbers  of  pneumococci  are  present.  The  disease  in  the 
suddenness  of  its  onset  and  in  the  extreme  gravity  of  its  nature 
U-ars  a  resemlilance  to  pneumococcal  peritonitis.  The  symp- 
toms often  (!evei..i>  wiih  li-htnii!;:  r,ii)i.i:ty.  ami  the  changes 
in  the  cerebrospinal  fluid  are  equally  sudden,  the  whole  char- 
;icter  of  the  tluiil  >ometinies  undcrgding  a  complete  transforma- 
tion in  -'4  hours. 

In  the  secondary  cases  the  primary  focus. may  1)C  found  in 
a  purulent  otitis  media,  or  in  such  a  pulmonary  condition  as  a 
localized  empyema.  The  onset  as  a  rule  is  not  so  acute,  but 
the  termination  is  the  same  as  in  the  primary  form. 

Opinion  varies  as  to  the  frequency  of  meningitis  as  a  com- 
plicatiim  of  pneumonia.  We-t  \>n\vA  no  case  in  a  series  of 
200.  but  Osier  records  S  per  cent,  of  cases  at  Montreal.  In- 
vasion of  the  subarachnoid  spnre  bv  the  pneumococcus  is.  how- 
ever, verv  much  more  frequent  than  the  statistics  regarding 


(8     riivsioi.or.v  and  p\tiioi.ogy  of  the  cerebrospinal  fluid 


iiKninKilis  would  lead  one  to  l)elicve.  Rohdenlnirj;  and  Van- 
der  \'ecr  have  established  the  fact  that  in  a  large  nuniher  of 
fatal  eases  of  pneunmnia  lumbar  puncture  will  reveal  the 
l)resence  of  pneuiuococci.  although  no  meningitis  may  be  pres- 
ent. In  a  series  of  cases  examined  irrespective  of  meningeal 
symptoms  they  found  that  in  the  cases  which  ultimately  proved 
fatal  pneunuicocci  were  ol)tained  in  culture  in  i<7  per  cent., 
wlvrcas  in  ca^es  which  recovered  only  34  per  cent,  were  posi- 
tive. The  positive  cases  all  gave  a  positive  globulin  reactiim 
and  an  increa.scd  cell  count.  In  only  one  case  was  the  tUnd 
l)urulent.  and  this  was  the  only  case  with  meningeal  symptoms. 
In  pneumococcal  meningitis  the  lluid  varies  to  an  even 
!;,-c:i;cr  e\:cnl  thrji  in  llie  meningococcal  form.  The  pres- 
sure is  raied,  the  ([uantity  of  tluid  increased,  the  protein  con- 
tent greatly  ni  e.vce  s,  and  the  tluid  may  be  highly  purulent. 
On  the  other  hand  it  may  be  so  clear  as  to  cause  grave  doubts 
as  to  wlui'.ier  a  meningitis  is  present.  I  have  withdrawn  a 
lluid  whic'i  to  the  nakc'l  eye  was  perfectly  normal,  but  when 
a  film  was  prenarod  in-n;  tb.c  luicenlrifuged  tluid  it  was 
foun.l  to  contain  large  numbers  of  pneumococci.  'Ihe  case 
(Ui-'d  a  l"e.\  i;a\-  lati.r  oi  tyj)ical  pneumococcal  meningitis. 

I'ilni-  are  to  Ik-  made  from  the  tluid,  and  stained  with 
methylene  blue  and  with  Gram's  stain.  The  predominant  cell 
i-,  ;1k'  ]).  .'.m-rph.  which  i>  u>ually  present  in  large  numbers. 
Occasionally,  especially  in  the  early  stages,  lymphocytes  may 
be  nuuKTous.  Cuhurcs  -hould  be  made  on  blood  agar,  but 
tlie  nioM  eii:;r;ic;eri-i!C  nvirphological  appearances  are  to  be 
ob-cr\td  in  ilie  organi-nis  in  the  smears. 

Tlie  -piiial  lluid  often  contains  an  increased  amount  of 
fibrin.  In  one  case  at  the  \Vinnii)eg  General  Ib.-pital  the 
tliiid,  which  wa-  in(en~ely  blood  stained,  clotted  into  a  solid 
ie]l\  -like  ma-s  w  ilbin  in  minutes  of  withdrawal.  The  clot  was 
a  s'cro-f:lirinonr~  one  in  which  red  corpuscle^  were  entangled, 
and  the  phenomenon  was  certainly  not  due  to  the  coagulation 
ol  lilood  already  present  in  the  Ihiid.  Smears  showed  large 
iium])ers  of  capsulated  diplococci,  which  on  culture  proved  to 
be  pneumococci. 


'm 


Streptococcal  Meningitis. 


MENINGITIS 


99 


STREPTOCOCCAL  MENINGITIS 

Primary  mcniiigea'  infection  with  the  streptococcus  is  a  rare 
occurrence.  Secondary  spread  of  an  inllanmiatory  process 
from  the  middle  ear  or  from  the  sinuses  of  the  skull  is,  on 
the  other  hand,  comparatively  frecpient. 

The  pathologic  findings  in  streptococcal  meningitis  arc  very 
similar  to  those  in  the  pneumococcal  f(jnn.  It  is  rare  to  en- 
counter a  clear  tluid.  The  polynuclear  leucocytosis  is  usually 
very  great.  The  organisms  are  present  in  tlie  form  of  chains, 
mainly  extracellular  but  sonie  intracellular,  and  are  readily 
recognized.  If,  however,  they  only  occur  in  diplococcal  foim, 
cultural  methods  must  be  adopted  in  order  to  separate  them 
from  the  pneumococcus. 

Several  varieties  of  streptococcus  have  been  described  as 
occurring  in  streptococcal  meningitis.  Of  these  the  strepto- 
coccus hannolyticus  is  by  far  the  most  frequent.  It  is  ac- 
tively h;eni(ilytic,  and  on  blood  agar  the  colonies  are  rapidly 
surrounded  by  a  clear  zone  where  h;cniolysis  has  taken  place. 

Next  in  frei|uency  comes  the  streptococcus  viridans.  On 
blood  agar  it  produces  a  green  color,  which,  however,  may  be 
confused  with  a  somewhat  similar  appearance  sometimes  seen 
in  the  case  of  pueumococci  growing  on  this  medium.  Growth 
in  blood  serum  i)tTers  a  ready  means  of  differentiation.  In 
the  fluid  medium  the  streptococcus  viridans  grows  in  long 
chains  of  jo  or  more  elements,  whereas  tiie  pneumococcal 
cliains  are  never  composed  of  more  than  0  to  8  elements. 

The  streptoccKcus  mucosus  may  be  found  in  sporadic  cases, 
generallv  secondary  to  purulent  conditions  of  the  middle  ear. 
Schotlmiiller  has  described  a  number  of  such  cases,  which 
invariably  proved  fatal.  The  organism  has  also  been  found 
in  one  or  two  small  epidemics  in  which  the  mortality  was  com- 
paratively low  —  from  40  to  50  per  cent.  It  is  readily  rec- 
ognized by  the  characteristic  capsule  which  surrounds  the 
chains,  and  by  the  slimy  growth  which  it  i)roduces  in  culture. 
On  blood  agar  it  forms  a  greenish  color  which  may  simulate 
that  of  the  streptococcus  viridans  or  the  pneumococcus,  but 


lOO        PUVSIOLOCV  AM)    I'ATHOLOGV  OF  THE  CnRKRROSIMNAI,   FLUID 

it  may  Iv  (liU'orciuiated  from  these  orj^aiiisms  hy  jjrowing  it 
al  Jjt     (    ,  at  wliit-li  tein])erature  no  color  i>  proilueetl. 

I'iiially,  the  streptococcus  putridus  has  been  descriheil  in 
one  or  two  ca.ses,  secondarv  to  an  infection  liy  tliis  organism 
elsewhere.  It  can  i)e  recognized  by  the  characteri-lic  odor  of 
the  cultures. 


TUBERCULOUS  MENINGITIS 

Apart  from  epidemics  of  cerebros|)inal  meningitis,  the  or- 
ganism most  fre(|uently  responsible  for  acute  inllammation  of 
the  meninges  is  the  tubercle  bacillus.  'I'ubcrcnlous  meningitis 
is  ])rol)ably  in  every  case  secondary  'o  some  ])riniary  focus 
elsewhere,  although  in  many  cases  it  is  extremely  difllcult  to 
find  such  a  focus.  It  m;iv  occur  a>  i)art  of  a  general  miliary 
tuberculosis,  or  mav  be  the  only  manife^t.niinn  nf  the  di.— 
semin.ilion  of  the  process.  ihcre  nia\'  be  w  idc>pread  tuber- 
culous inbltration  of  the  meninges  with  abninl.int  exudate  es- 
pecially at  the  base  of  the  brain,  or  a  few  scattered  tubercles 
along  the  line  of  tiie  Sylvian  vessels  only  discernible  with  the 
aid  of  ;i  magnifying  lens  ina\'  be  all  that  is  rewaletl  by  die 
autopsy. 

In  view  of  these  considerations  it  is  natural  that  the  condi- 
tion of  the  spinal  Ihiid  should  vary  considerably  in  different 
cases.  In  the  great  majority  of  cases  the  i)res>ure  is  niised, 
often  very  considerably  so.  It  u>ually  lies  between  joo  and 
400  mm.;  but  in  some  cases  may  rise  as  high  as  700  or  e\en 
Soo  mm.  A  normal  pressure  cannot,  howeser.  be  regarded 
as  conclusive  e\  idence  against  tuberculous  meningitis.  In 
the  later  stages  occlusion  of  the  foramina  in  the  ntof  of  the 
fourth  ventricle  may  occur,  with  the  production  of  a  condition 
of  internal  hydrocephalus,  and  ;i  couseijuent  di-;ippearance 
of  the  previous  high  pressure. 

The  iluifl  is,  as  a  nde,  clear  or  slightly  opalescent.  Only 
in  exceptional  cases  is  it  distinctly  turbid.  The  combin.ation 
of  a  high  cerebrospinal  ])ressurc  together  with  a  clear  fluid 
is  stronglv  suggestive  of  tuberculous  meningitis. 

When  the  lluid  is  allowed  to  stand  for  a  short  time  a  net- 


MliN'lNGlTIS 


lOI 


work  o  -  skein  like  a  fine  cobweb  forms,  which  appears  to  Im; 
su>pcnik(l  from  the  surface  of  the  lluid,  and  which  waves 
to  and  fro  as  the  tube  i>  moved.  This  appearance  is  highly 
characteristic,  althi)Uj,'h  not  absohitely  pathopiomonic  of  this 
condition.  It  thfters  from  tliat  seen  in  purulent  meningitis, 
in  which  the  coagulum  is  flaky  and  friable,  and  tends  to  ail- 
here  to  the  sides  of  the  tube,  it  is  essential  for  the  formation 
(if  this  clot  that  the  lluid  should  be  left  undisturl)e(l,  as  any 
agitation  will  ])revent  its  aj)])earance. 

An  increase  in  the  ])rotein  content  is  a  very  constant  feature 
of  the  tluid,  although  it  docs  not  reach  the  high  tigures  found 
in  the  other  forms  of  acute  meningitis,  varying  as  a  rule  be- 
tween O.I  and  0.3  per  cent.  In  a  few  cases  no  increase  can 
be  detected.  In  such  a  case,  bowe\er,  if  the  fluid  be  ex- 
amined on  a  --ubseiiuont  occasion  a  positive  reaction  will 
I)robablv  be  obtained  This  is  a  test  which  is  readily  per- 
formed at  the  beilside,  and  it  is  wise  to  go  armed  with  some 
I  in  JO  carbolic  or  ammonium  sulphate  solution. 

The  sugar  is  as  a  rule  decreased,  but  not  to  the  same  extent 
as  in  the  other  forms  of  meningitis.  In  some  cases  it  is 
present  in  normal  amount. 

MestRvat,  who  tends  to  somewhat  over-cmphasi;^e  the  im- 
portance of  a  purelv  chemical  examination,  maintains  that 
diminution  in  the  chlorides  and  increased  im])ermeability  to 
m'trates  are  two  of  the  most  characteristic  features,  lie  gives 
the  normal  chloride  content  of  the  fluid  as  0.74  per  cent.,  but 
finds  that  in  tuberculous  meningitis  it  varies  from  0.5  to  0.6 
per  cent,,  a  nnich  greater  reduction  than  is  found  in  the 
meningococcal  or  pneumococcal  forms.  The  permeability  to 
nitrates  is  determined  by  giving  the  patient  i  gram  of  sodium 
nitrate  for  everv  T,n  kilos  of  body  weight,  withdrawing  the 
fbiid  i,  hours  later,  and  e-timating  the  amount  of  the  salt 
present.  In  health  fnnn  o.S  to  1.0  per  cent,  is  obtained,  in 
cerebrospinal  meningitis  3.8  per  cent.,  and  in  tuberculous  men- 
ingitis from  .(.3  to  8.5  per  cent. 

In  ordinarv  routine  work  the  cell  count,  both  quantitative 
and  qualitative,  is  one  of  the  readiest  methods  of  diagnosing 


\02 


PHYSIOLOGY  AN'I)   PATHOLOGY  OF  THE  COREBROSPINAL  FLUID 


i      ^ 


tilt  romlition.  No  one  feature  is  pathognomonic,  Init  when 
tlie  result  is  taken  into  consideration  along  with  the  other 
laboratory  and  clinical  findings  a  correct  diagnosis  can  he 
arrived  at  in  the  grcnt  majority  of  cases.  The  cells  are  al- 
most always  increased  in  number.  This  increase  is  moderate, 
averaging  as  a  rule  from  50  to  200  per  c.mm.,  and  never 
reach.ng  the  enormous  figures  met  with  in  the  purulent  tluids 
of  the  other  forms  of  acute  meningitis.  In  very  exceptional 
cases  there  may  be  no  cellular  increase. 

The  differential  count  varies,  but  the  small  lymphocyte  is 
usually  present  in  great  excess.  The  centrifuged  film  often 
bears  a  close  resemblance  to  that  seen  in  tabes  dorsalis.  The 
same  appearance  is  seen  in  flms  made  from  the  pleural  fluid 
in  tuberculou.;  pleurisy.  Polymorphonuclear  leucocvtes  mav 
be  entirely  absent  or  only  present  in  -mall  numliers.  Occasion- 
ally, however,  they  may  cf|ual  or  even  exceed  the  lvni])hncvtes 
in  number.  Tn  a  few  such  cases  it  has  been  found  that  a 
secondary  infection  was  present,  u^nallv  the  meningococcus. 

In  -pccimens  prepared  by  the  Alzheimer  method  differen- 
tiation can  be  carried  further,  and  cell  forms  may  be  ob- 
served almost  as  manv  and  varied  as  in  syphilitic  infectioTis  of 
the  meninges.  Tailed  forms  and  rdtterzellen  may  Ix;  present, 
and  in  particular  large  numbers  of  macrophages.  Plasma 
cells  have  also  been  described. 

Tt  will  be  seen  that  although  any  of  the  above  pathological 
change-  may  In?  met  with  in  other  conditions,  vet  when  tliev 
are  considered  together  and  especially  in  relation  to  the 
clinical  condition  of  the  patient  it  will  usually  be  possible  to 
make  a  correct  diagnosis.  The  only  absolutely  certain  method, 
however,  is  the  demonstration  of  the  tubercle  bacillus.  This 
is  by  no  means  al\va\s  easy,  and  a  \ery  prolonged  search  may 
be  ncrc^-arv  before  a  single  organism  is  found.  The  results 
of  differt'nt  authors  \arv  from  50  to  100  per  cent.,  the>e 
v.-.riation-  probably  depending  on  the  care  in  tecbnic  and  the 
amonnt  of  time  spent  in  searching  for  the  bacilli.  \''arioiis 
n:rthnds  ha\e  been  suggc-tcd,  luit  far  the  simplest  and  most 
satisfactory  is  to  take  the  delicate  cobweb  which  forms,  spread 


,i 


I 


MENINGITIS 


103 


it  out  as  thinly  as  possible  upon  a  slide,  and  stain  with  carbol 
fuchsin.  If  bacilli  be  present  they  will  be  found  in  the  til)rin 
net-work. 

In  the  event  of  failing  to  find  any  bacilli  the  enrichment 
method  of  Tretnbur  may  be  used.  The  lluid  is  incubated  for 
from  24  hours  to  several  days,  at  the  end  (jf  which  time  a 
Sreat  multiplication  of  the  orj,fani.Mus  may  have  taken  i)lace. 
The  method  is  not  successful,  however,  in  every  instance. 
It  is  of  course  essential  that  every  precaution  against  con- 
tamination be  adopted,  otherwise  the  incubating  lluid  will 
speedily  liecome  turi)id. 

I'inally,  animal  inoculation  may  be  resorted  to.  The  long 
period  which  has  to  relapse  before  the  result  of  the  inoculation 
c;ui  be  deteriuined  may  be  !.',re;uly  reduced  l)y  .\-ra>ing  the 
guinea-pig  previous  to  inoculation.  This  interferes  so  nuieh 
with  the  resisting  power  of  the  animal,  proliably  owing  to  the 
effect  of  the  rays  on  the  lymphoid  tissue,  that  the  usual  period 
of  4  to  8  weeks  may  be  reduced  to  about  10  days.  The  centri- 
fuged  deposit  of  the  lluid  should  be  used  for  the  inoculation. 
A  recent  method  of  e.xamining  the  cerel)rospinal  lluid  in  cases 
of  suspected  tubc-culous  meningitis  is  that  of  Kasahara.  He 
only  records  5  cases  with  3  controls,  and  in  only  one  of  the  con- 
tnjis  (Hydrocephalus)  was  the  lluid  normal,  but  the  results  are 
so  striking  that  I  gi\e  them  here,  although  I  have  had  no  oppor- 
tunity of  conlimiing  them 

The  method  is  dependent  on  the  production  of  a  focal  re- 
action by  the  injection  of  tuberculin.  The  usual  amount  of 
cerebrospinal  fluid  is  withdrawn,  and  from  o.i  to  o.ooj  mg 
of  Koch's  old  tuberculin  diluted  with  normal  saline  to  i  c.c. 
is  injected  into  the  spinal  canal.  A  second  specimen  of  spinal 
fluid  is  obtained  24  hours  later,  and  the  two  Huids  compared 
as  to  cytological  and  chemical  reactions.  In  each  of  the  five 
cases  of  tuljerculous  meningitis  a  most  remarkable  cellular 
increase  was  observed.  The  lymphocytes  increased  in  one 
case  from  50  to  900,  polymorphs  appeared  in  considerable 
mnnbers,  but  the  niost  .striking  feature  was  the  liehavior  of 
the  red  cells.     In  every  case  large  numbers  of  red  cells  made 


I04       IMI^SIOI.Or.Y  AM)   I'ATIIOI.Or.^'  OF  Tlli;  CnRnnROSI'IN' \I.   Fl.l'ID 

their  appearance,  in  one  case  tlie  nnnihcr  rcacliin^  ,^-'(i<i  lur 
c.nini.  The  control  cases  sliowed  no  ri.'.'u-tiiin,  luit.  a>  Iia^ 
been  already  pointed  out,  far  more  extensive  cli-ir*  atimi, 
nin>t  he  nia;le  hefnre  (lefniile  ci>nclu-iiin>  ran  he  drawn, 
Kasahara  does  not  record  the  clinical  effect  of  the  tuliemilin 
iiijei'tion-;. 


'■  *  I 


.     .-1 


MENINGITIS  DUE  TO  OTHER  ORGANISMS 

'i"he  vast  niajiirity  of  cases  of  actito  incniniri'is  are  due  to 
the  meningococcus,  the  pncnmococcus,  the  streptoc(H-cU'^,  and 
the  tuliercle  !iacilhi>.  Occasionallv.  Imwever,  menint^itis  mav 
he  can-^ed  hy  one  of  a  very  lart^e  ntunlier  nf  diffcrt'iit  ori;aii- 
isms.  These  cases  will  l)e  briefly  considered.  When  a  definile 
inenin,i^iti>  is  pre-enl  the  u<ital  eerehm-piiKd  lliiid  iMidii;!;-^  .-mt 
present,  namely  tnrl>i(lity  i<\  xaryipi'  di'L^ree.  relhilar  increase 
C'-peeially  amontr-^t  the  p(i!\  nnelears,  marked  ,t;lnl,ulin  reactinn. 
and  diminntinii  in  the  F^'hlinq-  reduction.  That  is  m  sav.  the 
only  distini;-nishitv  feature  in  the^e  differetU  fornn  is  the 
presence  of  tlie  intectinj:^  oriranism. 

Staphylocnccal  meiiincfitis  is  much  rarer  than  miirht  he  ex- 
pected. It  mav  occur  in  a  staphylococcal  septica-mia.  or  mav 
be  secondary  to  infection  following:  injury  of  the  >kull.  The 
orsjanisms  are  jiresent  in  very  sm.all  numhers.  and  can  with 
difficulty  be  found  in  smears.  If  only  found  in  cidture  con- 
tamination from  the  skin  or  the  tissues  of  the  hack  must  he 
carefully  excluded. 

Menin<jitis  may  he  caused  hy  the  typlioid  bacillus.  In  mauv 
cases,  however,  the  ororanism  may  be  present  in  the  fluid 
without  causin_c;  a  meninj^itis.  just  as  it  mav  occur  in  the 
urine  without  settinp^  up  a  cystitis.  T'urther,  menint^Htic 
symptoms  may  be  produced  by  l>acilli  circulating^  in  the  blood 
without  a  correspoudinjif  infection  of  the  cerebrospinal  llnid. 
In  these  cases  lumb.ar  puncture  will  reveal  nothinjj  more  than 
a  somewhat  increased  pressure.  ^lenini,dtis  due  to  para- 
typhoid bacilli  has  also  been  described. 

Infection  of  the  subarachnoid  .sac  by  the  bacillus  coli  some- 
times occurs.     I  have  ob.scrved  such  a  case  in  a  girl  of   12, 


MKNINr.lTIS 


105 


who  was  suffcrinj^  from  Uoud  infec'.ion  with  the  same  or- 
ganism. Persistent  headache  with  shght  head  retraction  siij;- 
gested  the  possibility  of  meningitis,  l)Ut  lumhar  punctnre  re- 
vealed a  clear  tluid  with  no  cellular  and  only  a  slight  globulin 
increase.  In  the  films  were  a  number  of  (iram-ncgative 
bacilli,  whiih  on  further  investigation  jjroved  to  be  bacillus 
coli.  'J'hc  rtuid  was  examined  on  more  than  half  a  do/en 
occasions,  and  the  bacilli  were  present  on  each  occasion  until 
convalescence  set  in,  when  they  finally  <lisappeared. 

Other  org,ini-ms  which  have  been  described  are  the  in- 
fluenza bacillus,  the  bacillus  pyocyaneus,  the  anthrax  bacillus, 
I'riedlimder's  pnenniobacillus,  the  bacillus  mallei,  actinomyccs. 
and  a  stre])tothrix.  In  general  paralysis  the  spirocheta  |)allida 
has  been  (UniMii-trited  by  injecting  the  ^^pinal  thiid  into  the 
testicle  of  the  rabbit.  I  have  examined  Alzheimer  prei)ara- 
tions  from  such  Ihiids  by  the  Levadili  method,  but  have  failed 
to  detect  aiiv  org.ini>ms.  Trypanosomes  are  constantly  pres- 
ent in  slcc])ing  sickness.  In  several  cases  of  chorea  the 
(li])loC(iccu>  rlicuiualicus  of  I'oyntou  and  I'aine  has  been  found 
in  the  spinal  tluid.  An  appreciable  rpiantity  of  toxin  has 
been  demonstrated  in  cases  of  tet;inus,  but  no  bacilli  are  ])res- 
cnt. 


SEROUS  MENINGITIS 

In  the  varieties  of  meningitis  discussed  up  to  the  present 
we  h;ive  been  dealing  with  intlanimatory  conditions  of  the 
meninges  in  which  a  definite  intlanimatory  exudate  is  present, 
and  in  which  the  infecting  organism  is  present  in  ihe  cerebro- 
s|)in;il  tluid.  In  ])r;ictice.  however,  cases  are  constantly  being 
met  with  in  which  the  symptoms  are  highly  suggestive  of 
meningitis,  but  the  cerebrospinal  tUiid,  which  is  invariably 
sterile,  gives  little  or  no  support  for  such  a  diagnosis. 
Should  such  cases  come  to  the  autopsy  table  no  evidence  of 
meningitis  can  be  found. 

This  condition  has  lieen  described  under  many  different 
names,  and  a  considerable  amount  of  confusion  exists  in  re- 
gard to  it.     Schottmiiller  describes  two  separate  conditions, 


I(/)        IMrVSI()I.(M,Y    AM)    PATIIOI.OCV   OF   TMR   CM  RKBROSPINAl     ."(.UiD 


*f 


f'f    '  i 


cirnim>iril.i'(I  ini'ii-tiims  iiioiiini,'itis  and  syinpallictic  lucn- 
iiij^itis.  Kaplan  speaks  of  iion-micotic  tncniiij^itis,  and  otlicr 
antlicirs  nsi-  >iill  diiYircnt  tiTnis.  The  term  senuis  tneninf^itis 
or  inenin.i,dtis  sero'<a  is  an  old  one.  and  if  hy  it  we  understand 
all  tliosf  cases  in  which  there  is  ineninijeal  irritatiun  withont 
a  definite  inflaniniation  of  the  nicninijes  it  appears  as  satisfac- 
tory a  one  as  can  he  devised.  Whatever  term  is  used  it  must 
he  .-ufficiently  ela-lie  ti>  include  a  ennsiderahle  variety  of 
conditions,  fur  the  enndition  i^  one  which  ma\'  ap|)ear  in  a 
nunilicr  nf  widcJN  ditYeriuf^  niorhid  states.  It  is  (.nly  intural, 
therefore,  that  tlie  cerehrospinal  l1uid  should  prestnl  cor- 
responding,' differences. 

One  of  the  most  important  causes  of  mcninc,dtis  scTo-a  is 
the  iire-eiicc  in  the  neiphhorhood  of  the  arachnoid  s;ic  of  a 
focu-  of  inllanuuaiion.  'i'his  fociN  is  situated  nv^t  conunonly 
in  the  middle  ear,  and  on  that  account  the  condition  is  one  of 
speci.d  imjtortance  to  the  aural  siu;t,'con.  Any  innaiumatory 
condition  of  the  >kull  may,  however,  ^ive  ri-^e  to  it.  A  deep- 
seated  abscess  of  the  hrain  mav  remain  uncomplicated  hy  a 
purulent  mem'ui,utis  for  a  coiisiderahle  time,  hut  symptoms  of 
a  serous  meniny;itis  may  make  their  appearance  at  a  much 
earlier  date.  .\t  .any  time,  of  course,  a  serous  meninjjitis  may 
develop  into  a  ptuailent  meninijitis,  should  the  infectious 
process  reach  the  pia  mater.  The  meniiii^dtis  in  these  cases  is 
evideiUlv  toxic  in  natiu'e.  the  toxins  hut  not  the  ori^anisms 
jrauurif^  access  to  the  meninp;es.  \'ery  truich  the  -ame  phe- 
nomenon is  seen  in  the  case  of  a  suh-diaphraijiuatic  ahscess. 
in  which  a  non-purulent  pleurisy  is  set  u])  hy  the  passa.c;e  of 
toxins  throuy;h  the  diaphraEjm. 

Another  preat  clinical  p;roup  in  which  serous  mcnini:;;itis 
may  appear  as  a  complication  is  that  of  the  infections  fevers, 
and  other  conditions  in  which  hacteria  and  their  toxins  cir- 
culate in  the  Mood.  Thus  the  symptoms  may  arise  in  the 
course  of  measles,  influenza,  tv])hoid,  pnetmionin,  and  rheu- 
n\atic  fever.  The  symptoms  of  lueninc^eal  irritation  not  infre- 
(luetitly  occtn-ring  in  mumps  should  possibly  be  classed  under 


MENINCITIS 


107 


this  hcailinp.  Cases  of  sunstroke  with  high  intracranial  pres- 
sure prol)al)Iy  furnish  still  another  example.  The  condition 
often  called  nieninpisnms  may  he  included  here.  Tt  is  merely 
one  variety  of  the  general  condition  serous  mcninRitis. 

Tn  many  cases  it  is  prohahle  that  the  full  force  of  the  ir- 
ritant falls  not  on  the  meninges  hut  on  the  ependvma  of  the 
choroid  plexus,  the  immediate  result  l)eing  a  greatly  increased 
production  of  cerebrospinal  fluid,  which  may  otherwise  he  per- 
fectly normal.  Quincke  records  several  such  cases  in  which 
hydrocephalus  was  assticiated  with  great  thickening  of  the 
ependvma  and  degenerative  changes  in  the  choroid  plexus,  hut 
in  which  the  meninges  showed  no  change.  Tie  also  suggests 
that  in  some  cases  there  may  he  a  coiulition  of  angio-neurotic 
rrdema  of  the  choroid  plexus,  thus  explaining  the  sudden  onset 
which  mav  occur  on  several  occasions.  This  is  one  of  those 
theories  which  it  is  as  difficult  to  disprove  as  to  prove. 

During  an  epidemic  of  meningococcal  meningitis  amongst 
the  British  troops  in  France  1  encountered  a  nimiher  of  cases 
which  were  apparently  serous  meningitis,  of  which  the  follow- 
ing is  tvpical.  The  patient  had  heen  feeling  ill  for  two  dav^. 
When  T  saw  him  he  had  marked  siens  of  meningitis  —  head- 
ache, head  retraction,  pain  in  the  hack  and  neck,  greatly  ex- 
aggerated knee  jerks,  and  a  marked  Kernig's  sign.  The  tem- 
perature was  104.4"  P.,  the  pulse  loR.  and  the  hlood  showed 
a  leucocytosis  of  T.^.400.  The  cerebrospinal  fluid  was  under 
ver>'  high  pressure,  issuing  in  a  forcible  stream  from  the  needle, 
but  it  was  quite  clear,  showed  no  cellular  nor  glolnilin  increase, 
and  was  sterile.  The  lumbar  puncture  at  once  relieved  the 
symptoms  of  intracranial  pressure  in  a  remarkable  wav,  and 
two  (lavs  later  the  patient  was  convalescent.  T  came  across 
several  similar  cases,  in  some  of  which  a  moderate  lympho- 
cytosis was  present,  but  in  no  case  were  there  any  organisms 
in  the  fluid.  Other  cases  from  the  same  battalion  with  identi- 
cal svmptoms  showed  piinilent  spinal  fluid  containinjr  large 
numbers  of  meninirococci.  The  only  conclusion  possible  is 
that  in  the  first  set  of  cases  the  organisms  were  circulating  in 


io8 


1'MYSIOI.OCV   ,\M>   I'\TII0I.(H;V   ny  TIM:  CI  RIIIROSI-IN  Al.   KI.LII) 


the  I)I()0(1.  but  only  tl'c  toxins  gained  access  to  the  cerehral 
nuMiinjjes.  -Ilu'  pm-iinsis  in  tlu-  u\»  cla>>e>  oi  eases  was 
entirely  difYerent. 

The  symptoms  are  essentially  those  of  increased  intracranial 
P'-'-ssure,  of  which  the  most  constant  is  headache.  ("he  cere- 
brospinal pressure  is  invariably  raise.l,  sometime^  t..  a  markol 
dej,'ree.  In  very  many  cases  the  lUiid  is  pcrtirtlv  clear,  and 
may  present  no  ..tlur  abnormality.  'Hie  omibinatiun  n\  a 
normal  llnid  under  bi-li  proure  with  the  Mini.lom.  of  nun- 
inpitis  is  almost  pathognomonic  of  serous  nieiiin-itis.  It  i^ 
well  to  bear  in  mind,  however,  that  in  the  very  e;.rliest  s-.-i^res 
of  acute  nienin-iiis  the  tlnid  may  occa-ioiially  -.|„,\\  but  lit'tle 
chant,'e. 

ft  IS  in  younj,'  children  that  the  most  important  manitVsta- 
tioiis  of  serous  nunin-ilis  are  met  uith.      A  eliild  may  present 
all  the  symj)toms  of  acute  menini^rjtis  such  as  vomitin.t,r.  rit,Mdity, 
head  retraction.   Kerniir's  si.r,,.  ap,]  bnbnn-  of  t!ie  foutan-lle. 
but  ihe  -pirri!  tluM  may  du.w  no  abuormalilv  except  eNtrenielv 
high   pressure.      In   such  ca-es   withdrawal'of  a  omsi,Ierable 
quantity  of  fluid  will  be  followed  by  remarkable  an.l  iunnediate 
clinical  improvement      The  symptoms  may  return  in  the  course 
of  a  few  days  or  weeks,  but  a  second  puncture  will  i)robablv 
restore  the  child  to  a  normal  condition.     The  ependyma  h.as 
apparently  been  stimulated  to  over-acli\  itv  bv  ,s<ime  toxin  cir- 
culating in  the  blood,  with  a  resullin-  excessive  production  of 
cerebrospinal  duid.  but  when  the  excess  of  fluid  has  been  re- 
moved a  condition  of  equilibrium  seems  to  be  established,  and 
the   danger,    undoubtedly   .cfreat    in    these   youu-   patients,    is 
averted.     The  condition  is  of  njreat  practical  importance,  and 
is  not   jjenerally   recoj^nized.     .Almost   all   the  cases   ..vhich    I 
have  seen  have  been  in  children  mider  one  vear  of  ,i-;e.     The 
most   important   sin.cflc   si.ijn    is    fullness   and    bidt,'iuj  of  the 
fontanelle.     The  fluid  should  be  withdrawn  until  the  fontanelle 
is  depres.sed 


MENINGITIS 


lOQ 


KKi'i'.ki.Ni  i:s 

Arzt  ami  llocsc;  Ihcr  I'aialyplmsmcniiijjitis  iiii  Kindesaltcr. 
\\  liner  kliii.   W  nct'i  i\-.ilir.    |i)<>S.   No.  7. 

fariK'Kit'  I)ick>oii,  W.  K. :  C'crcbrospitial  meningitis,  lirit.  Med. 
Jiinr.   |i)i7,  p.  454. 

IKiiiiaii    ami     i\  IcNliin :     .Miiiiniincciccal     .Miiiin^jitis.     I.ippiiicott, 

"J'.V 

llorilci.     r.     I.:     (■iT>lirii--|iin;il     livir.     ()xl'iii(l    iiKdical    pulilica- 

tioiis.   Hji.S.  p.  .S-*. 

Inilliloii,  A.  r. :  A-iptic  iiKniii;,'itis  followini,'  iiitratliccal  injection 
of  antititanic  sirnni.     Jimr.   R.  A.  M.  ('.,  XX\  I.  Xo.  2,  p.  -J34. 

K, III), 111 ;     Sir(il.iL;\  (if  lu'i'Miit^  ami  niiiita!  ili-ca'-i-.  )).  <)-'• 

K.'is.'iliara,  M.:  The  specific  (liai,'m)sis  of  tul)erciilmis  nieninijitis. 
Am.    Iiinr.   Di-.  (liild.   Kjlj,  XIIl,  p.   141. 

l.ariicli.  I  I.  and  I'i'jmit.  ].;  Siii,'ar  in  ihe  ciTclirospinal  thiid  in 
aciile  nieni:iL;iti>.  I'.iris  Medical.  \i)ij.  \'II.  .Xo.  15,  p.  ji)^.  ( fjuoted 
ill    luur.   .\iii.  Med.    \>mic.    ii>I",  I. Will.  p.   lofx).) 

''der:      I'racliee  of  medieiiu'.  Jlli   ediliim.   pp.    ^^^(1,    ^00,    :S|. 

Ouincke:  Meningitis  .^^erosa.  Samnil.  klin.  X'orte.,  I.eipz.  iSo.V 
Xo.  67.     Iiui.  Med..  _',v  ')55. 

Stewart.  I'lirves:  |)ia'.;m)^i-  of  ncr\ons  diseases.  .Arnold,  3r(l 
edition,  p.  441. 

Trcniliiir:  Die  Oniuckesclie  lainihalpiinktion  liic  der  F.rkcn- 
nnnp:  der  Meiiinjjitis  tuberculosa.     Klin.     Jahrlnich,   1910,  XXIV,  p. 

Vincent  and  Hellot :  Xonvelles  reclierclics  snr  le  precipitn-diap- 
nostic  (le  la  nieninijite  cereliro-spinalc.  Ridl.  et  mem.  Soc.  med. 
(Ics  Hop.  de  I'aris    i()(k),  XX\'TI,  p.  o.^-- 

Warrinijton,  \\".  I?.:  Intracranial  scrons  cfTusions  of  inflamma- 
tory orij;iii.     Ouart.  Joiir.  of  Medicine,    i()i4,  \'II,  p.  93. 

West :  X'ervons  phenomena  in  pneumonia.  Clin.  Journal,  1908, 
XXXI,  p.  364. 


■■*■<■! 


CHAPTER  XV 

SYPHILIS  UF  THE  x\ERVOUS  SYSTluM 

In  tlic  recent  history  uf  clinical  medicine  no  more  remarkable 
revolution  of  ideas  has  taken  place  than  in  the  case  of  the  re- 
lationship of  syphilis  to  the  nervous  system.  John  Hunter 
taugiit  in  1790  that  syphilis  never  affected  the  internal  organs, 
and  ni  those  days  the  paralysis  which  occasionally  followed 
syphilis  was  usually  attributed  to  the  mercurial  treatment. 

We  have  for  long  known  that  certain  pathological  lesions  of 
the  central  nervous  system  such  as  gummata,  arterial  degenera- 
tion, and  some  fomis  of  meningitis  are  syphilitic  in  nature. 
It  was  also  recognized  that  some  relation  existed  between 
syphilis  and  general  paresis  and  tabes  dorsalis  —  diseases 
which  were  called  para  or  metasyphilitic  —  but  the  exact  na- 
ture of  the  relationship  was  by  no  means  clear.  Many  au- 
thors refused  to  admit  that  syphilis  was  the  sole  etiological 
factor  in  these  diseases,  although  they  admitted  that  it  played 
a^  ver>-  important  part.  Even  so  eminent  an  authority  as 
Xonne  said  — "  At  the  outset  I  desire  to  make  it  clear  that 
progressive  paralysis  is  not  a  specific  syphilitic  disease  of  the 
brain."  The  demonstration  by  Xoguchi  and  Moore  of  the 
spiroch.Tta  pallida  in  the  brain  and  curd  in  general  paralysis 
and  tabes,  together  with  the  evidence  furnished  by  the  Wasser- 
inann  reaction  in  the  blood  and  the  spinal  fluid,  has  swept 
away  the  last  lingering  doubt.  It  is  now  universally  recog- 
nized that  there  is  but  one  neuro-syphilis  which  may  attack  the 
meninges,  the  blood  vessels,  the  nerve  cells  of  the  cerebral 
cortex,  or  thj  nerve  fibers  in  the  posterior  columns  of  the  cord. 
So  much  is  generally  granted. 

Recent  work  has,  however,  thrown  most  important  light 
on  tile  question  of  the  involvement  of  the  nervous  svsteni  in 


Lv.' 


SYPHILIS   OF  THE    NERVOUS   SYSTEM 


III 


the  earlier  stages  of  syphilis.  It  is  now  recognized  that  it  is 
not  the  case,  as  was  formerly  supposed,  that  nervous  syphilis 
is  necessarily  a  late  manifestation  of  the  disease.  The  whole 
tendency  of  the  work  of  the  past  few  years  has  been  to  throw 
ever  earlier  the  period  at  which  the  nervous  system  may  be- 
come infected,  until  we  have  reached  the  stage  where  cases 
are  being  reported  in  which  the  cerebrospinal  fluid  shows 
changes  said  to  be  characteristic  at  the  same  time  as  the  ap- 
pearance of  the  primary  sore. 

Although,  however,  it  is  wise  to  maintain  a  critical  attitude 
regarding  the  significance  of  certain  results,  there  is  no  room 
for  doiiDt  that  the  light  thrown  upon  the  whole  subject  of 
ncuro-syphilis  by  these  recent  investigators  on  the  cerebro- 
spinal fluid  is  of  the  very  greatest  importance.  It  is  certain 
that  in  the  general  systemic  infection  which  marks  the  com- 
mencement of  the  secondary  stage  the  nervous  system  not 
only  is  not  exempt,  but  is  in  reality  one  of  the  parts  of  the 
body  most  frequently  involved.  In  the  present  state  of  our 
knowledge  we  cannot  say  which  of  these  cases  will  speedily 
clear  up  and  which  will  develop  into  incurable  parenchymatous 
syphilis,  nor  do  we  know  the  factors  upon  which  this  depends. 
Further  work  may,  however,  serve  to  elucidate  these  verv  im- 
portant points.  From  the  practical  point  of  view,  all  cases 
showing  changes  in  the  spinal  fluid  should  receive  energetic 
treatment  until  the  fluid  has  returned  to  normal,  whether  or 
not  symptoms  of  nervous  disease  have  been  present,  .^s 
Xeisser  said  at  the  International  Medical  Congress  in  1913,  no 
one  should  be  passed  as  cured  of  syphilis  until  the  cerebro- 
spinal fluid  has  been  examined  and  found  normal,  and  those 
whose  experience  in  the  treatment  of  syphilis  is  most  extensive 
will  be  most  likely  to  agree  with  him. 


EARLY  SYPHILIS 

The  strong  tendency  at  present  is  to  place  the  possihilitv  of 
svphilitic  involvement  of  the  nervous  svstcm  at  an  ever  earlier 
date.  The  old  view  that  the  nervous  lesions  were  essentially 
late  manifestations  of  the  diseases  occurring  in  the  tertiary 


112        PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


i'. 


',■* 
K-.! 


^i' 


■  1 


I 
I 


and  post-tertiary  stages  has  Keen  replaced  In  the  modern  one 
that  the  central  nervous  system  may  be  one  of  the  first  organs 
to  be  invoKed.  CIregory  and  Karpas,  Gowers,  Xonne,  and 
many  others  have  piibhshed  cases  in  which  the  nervous  system 
became  involved  within  a  year  of  the  primary  infection.  In  a 
series  of  22  cases  of  secondary  syphilis  Dreyfus  found  changes 
in  the  spinal  fluid  in  17. 

In  these  secondary  cases  the  changes  in  the  fluid  usually 
noted  are  a  moderate  lymphocytosis  and  an  increase  in  the 
globulin.  In  the  majority  of  these  cases  the  Wassermann 
reaction  is  negative,  although  it  may  be  strongly  positive  in  the 
blood.  .-\  positive  Wassermann  in  the  spinal  fluid  indicates  a 
mucli  more  serious  involvement  of  the  nervous  tissue  than  a 
mere  pleocytosis  and  globulin  excess.  In  all  cases,  however, 
it  is  well  to  accept  the  cellular  and  globulin  changes  as  evidence 
of  direct  involvement  of  the  nervous  system,  even  with  a 
negative  Wassermann. 

That  cerebrospinal  involvement  in  secondary  svphilis  is  com- 
mon is  now  tmiversally  admittcil.  but  it  ajjpears  that  this  in- 
volvement may  be  earlier  still,  for  in  a  numlicr  of  cases  char- 
acteristic changes  have  been  found  in  the  fluid  in  the  primarv 
stage,  although  a  positive  Was^^ermann  reaction  has  never  been 
present.  Wile  and  Stokes  descril)e  6  primary  cases,  in  4  of 
which  the  spinal  ftuid  was  abnormal,  one  case  showing  a  cell 
count  of  20n.  Fruhwald  and  Zalozioki  funiish  even  more 
striking  evidence  of  early  infection,  for  bv  injecting  the  cere- 
brospinal fluid  into  the  testicles  o,"  rabl)its  tliev  demonstrated 
the  presence  of  the  spirochreta  pallida  in  both  primarv  and 
secondary  syphilis.  In  some  of  these  cases  there  were  nervous 
svmptoms.  in  others  there  were  none.  This  final  confirma- 
tion of  the  diagnosis  by  the  demonstration  of  the  spirochreta 
pallida  in  the  cerel)rospinal  fluid  has  now  been  made  by  a 
nimiber  of  workers.  Txvaditi.  Marie  and  P.ankowski  suc- 
ceeded in  finding  the  spiroch.Ttes  in  the  centrifuged  ventricular 
fluid  of  a  ca-e  of  general  paresis,  and  \\'ile,  who  was  successful 
with  inoculation  tcst-^  in  over  60  per  cent,  of  a  series  of  8  cases, 
including  secondary   syphilis   involving  the   nervous   svstem. 


SYPHILIS  OF  THE   NERVOUS  SYSTEM 


113 


tal)e.s  dorsalis,  and  general  paresis,  believes  that  the  spinal 
lluid  contains  spirocha'tes  at  certain  times  in  every  case  of 
neuro-syphilis. 

CEREBROSPINAL  SYPHILIS 

This  term,  although  admittedly  unsatisfactory  in  the  light  of 
present  day  knowledge,  has  passed  into  such  general  usage  that 
it  is  difficult  to  dispense  with  it.  By  it  we  include  all  fonns  of 
what  Mott  has  termed  interstitial  syphilis,  that  is  to  say  cases 
in  which  the  parenchimatous  elements  of  the  nervous  system 
are  not  primarily  involved.  The  three  principal  types  are  the 
gumma,  syphilitic  endarteritis,  and  syphilitic  menigitis  or 
meningo-encephalitis. 

The  cerebrospinal  pressure  is  as  a  rule  above  normal  and  a 
globulin  reaction,  sometimes  very  marked,  is  almost  always 
present.  A  somewhat  less  constant  feature  is  a  cellular  in- 
crease, which  in  the  meningitic  form  may  reach  several 
thousand.  Where  the  only  lesion  is  an  endarteritis,  however, 
the  pleocytosis  may  be  slight  or  even  entirely  absent.  The 
characteristic  cell  is  the  small  lymjjhocyte.  In  cases  of  acute 
syphilitic  meni,!,ntis,  howeve.,  in  which  the  reaction  is  very 
marked  the  spinal  lluid  may  show  considerable  numbers  of 
endothelial  cells,  and  in  some  cases  polymoq:)hs  form  a  notice- 
able feature  of  the  cell  picture. 

Regarding  the  Wassermann  reaction  in  this  condition  the 
results  of  different  workers  in  the  past  have  varied  to  a  marked 
degree.  The  earlier  Cierman  workers,  using  the  original  Was- 
sermann  technic,  regarded  a  negative  finding  in  the  spinal 
lluid  as  the  rule.  Plant  found  a  jjositive  reaction  in  only  6 
per  cent,  of  his  cases,  and  even  in  these  the  reaction  was  re- 
garded as  the  exception  rather  than  the  rule.  The  substitu- 
tion of  tlie  more  sensitive  cholestcrinised  heart  antigen  for 
the  sy])hilitic  liver  antigen  of  the  original  method,  and  the  in- 
troduction of  the  use  of  larger  fjuantilies  of  fluid  up  to  10 
or  even  J.o  c.c,  have  resulted  in  a  great  change  of  attitude 
on  this  subject.  Mcintosh  and  Fildes,  it  is  true,  condemn  the 
use  of  large  (luantitics  of  fluid  on  the  ground  that  non-specific 


114        PHYSIOLOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


tj 


4ii 


f  ii 


I 


reactions  may  be  obtained,  and  claim  that  by  using  choles- 
terinised  heart  as  an  antigen  they  can  obtain  a  very  high  per- 
centage of  positive  resuhs  with  the  use  of  0.2  c.c.  of  fluid. 

Most  workers  agree,  however,  that  the  use  of  larger  ciuan- 
tities  is  essential  if  a  true  estimate  of  the  condition  of  the  fluid 
in  cerebrospinal  syphilis  is  to  be  arrived  at.  In  many  cases  a 
positive  reaction  will  only  be  obtained  when  i.o  c.c.  of  fluid 
is  used,  and  there  is  no  good  reason  to  believe  that  such  quan- 
tities will  give  a  non-specific  reaction.  Sometimes  a  cellular 
and  globulin  increase  will  be  found  in  cases  of  secondary 
syphilis  even  when  no  nervous  symptoms  are  present.  In  such 
cases  a  negative  reaction  will  invariably  be  obtained  when 
O.J  c.c.  of  fluid  are  used,  but  with  i.o  c.c.  the  reaction  may  be 
positive.  It  is  obvious,  therefore,  that  many  positive  reactions 
will  be  missed  if  only  0.2  c.c.  of  fluid  are  used.  The  en- 
darteritic  form  of  cerebrospinal  syphilis  may  however  give  a 
negative  reaction  even  when  the  full  quantity  is  used.  The 
Auszi'crtmujsvicthodc  further  provides  a  very  useful  indica- 
tion as  to  the  success  of  treatment  and  the  progress  of  the 
case,  for  by  it  the  gradually  decreasing  intensity  of  the  reaction 
can  be  accurately  measured.  If  a  fluid  gives  a  strongly 
positive  reaction  with  o.i  c.c.  at  the  l)eginning  of  treatment, 
and  at  the  end  J.o  c.c.  are  necessary  in  order  to  obtain  a 
positive  result,  it  is  evident  that  the  therapeutic  effort  has  been 
of  some  avail,  l-'inally,  in  an  untreated  case  the  amount  of 
fluid  which  it  is  necessary  to  use  in  order  to  obtain  a  posi- 
tive reaction  affords  a  very  fair  indication  as  to  the  nature 
of  the  lesion.  If  1.0  c.c.  or  2.0  c.c.  are  necessary  the  ca.se  is 
almost  certainly  one  of  cerebrospinal  syphilis.  In  general 
paresis,  on  the  other  hand,  a  positive  reaction  will  be  obtained 
with  0.05  c.c.  or  even  with  less.  Tabes  dorsalis  occupies  an 
intermediate  position. 

The  colloidal  i^iM  test  will  often  show  a  reaction  in  the 
mid  or  so-called  luetic  zone. 

In  the  difticult  task  of  diffcrentiatint;  between  general 
paresis  and   cerebrospinal   syphilis   the  thercpeutic  test  often 


i'',l 


:.-(; 


V\ 


u 


% 


Lymphocytosis  in  General  Paresis. 


SYPHILIS  OF  THE   NERVOUS  SYSTEM 


IIS 


yields  information  of  great  value.  One  or  two  intravenous 
injections  of  salvarsan  will  usually  produce  little  or  no  effect 
on  the  spinal  lluid  in  general  paresis,  although  prolonged  in- 
traspinal injections  by  the  Swift-Ellis  method  may  ultimately 
cause  considerable  improvement.  In  cerebrospinal  syphilis,  on 
the  other  hand,  the  results  of  ordinary  specific  treatment  are 
often  remarkable,  the  change  being  most  marked  in  the  number 
of  lymphocytes,  which  may  fall  to  normal  in  a  comparatively 
short  time.  Walker  found  that  in  cases  of  syphilitic  meningitis 
in  which  endotlielial  cells  were  numerous  these  cells  were 
the  first  to  show  a  marked  decrease  in  response  to  treatment, 
followed  later  by  a  fall  in  the  small  lymphocytes.  The 
globulin  reacts  to  a  lesser  extent.  The  Wassermann  is  the 
most  resistant  of  the  three  reactions,  but  with  intensive  sal- 
varsan treatment  it  also  may  be  reduced  or  entirely  abolished 
even  when  i  c.c.  of  fluid  is  used.  Occasionally,  however,  the 
Wassermann  may  respond  more  readily  than  the  globulin. 
This  may  occur  in  any  of  the  forms  of  neuro-syphilis. 

TABES  DORSALIS 

As  regards  the  condition  of  the  cerebrospinal  fluid  tabes 
occupies  a  position  midway  between  cerebrospinal  sj-philis  and 
general  paresis.  The  most  constant  feature  is  a  lymphocy- 
tosis, moderate  in  degree,  ranging  from  60  to  100.  Such 
an  increase  is  present  in  about  90  per  cent,  of  cases.  In  very 
old-standing  cases  the  increase  may  be  so  slight  as  to  leave 
room  for  doubt.  .Alzheimer  sections  show  the  chief  type  of 
cell  to  be  the  small  lymphocyte.  In  many  cases  no  other  cell 
can  be  found.  Large  mononuclear  or  endothelial  cells  may 
occur,  but  I  have  never  found  plasma  cells,  although  they  are 
described  by  some  authors.  In  quiescent  cases  polymorphs 
are  as  a  rule  not  found,  but  if  the  fluid  be  examined  during  or 
immediately  after  a  crisis  they  may  form  a  considerable  por- 
tion of  the  cell  count.  At  these  times  the  total  amount  of 
fluid  becomes  much  increased,  and  the  globulin  excess  is  also 
more  apparent.     The  nature  of  such  crises  is  not  well  un- 


t'i 


II 


,  ,6       PHYSIOLOGY  AXD  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

derstood,  but  the  changes  in  the  sphml  lluid.  especially  the  ap- 
pearance of  poly.ncrplvs  are  strongly  suggestive  of  meningeal 

"  Glolnllin  is  verv  constantly  increased,  but  not  to  the  extent 
seen  in  paresis,      l-ehling  reduction  is  normal. 

The  results  of  the  Wassermann  test  vary  with  d.l  ercnt 
workers.    .Icpending   lu)   doul.t    upon    the   method   employed. 
M.,st  worker.,  obtain  positive  results  in  from  50  to  70  per  cent, 
of  ca.es.     llauptmann  by  his  "  .\uswertungsinetho<le      got  a 
positive  reaction  in  almost  every  case,  whilst   Mcintosh  and 
Fildes  using  0.2  c.c.  in  a  small  series  had  .>>  per  cent,  ol  posi- 
tives,    if  Muntities  up  to   ..o  c.c.  be  used,  together  with  a 
ehole.teriniscu  heart  antigen,  a  positive  reaction  will  1k^  ol,- 
tained  in  from  .So  to  90  per  cent,  of  untreated  cases,  or  even 
hi-her      The  reaction  in  the  blood   is  positive  in  about  the 
same  percentage  of  cases  as  in  the  tluid.  but  it  is  important  to 
hear  in  mind  that  the  reaction  may  be  positive  in  the  serum 
and  negative  in  the  tluid.  or  positive  in  the  tUnd  and  negative 
i„  the  .eruni.     I'or  this  reason  it  is  essential  in  all  cases  to 
examine  both  the  serum  aiul  the  tluid.     To  sum  up  the  p.)sition 
with  regard  to  taints,   if  a  patient   with   suggestive  physical 
signs  has  an  increase  in  cells  and  globulin  and  a  positive  W  as- 
scrmann  in  the  spinal  tluid  or  the  bloo.l  or  in  l)oth.  there  is 
ample  evidence  for  a  positive  diagnosis.     With  a  negative  re- 
action in  both  blood  and  spinal  tluid  there  may  l>e  some  hes- 
itancv   an.l  the  therapeutic  test  may  have  to  be  applied.      I  he 
presence  of  plcocytosis  and  globulin  increase,  however,  in  a 
chronic  case  showing  evi.lence  of  involvement  of  the  nen-ous 
system  may  be  taken  as  almost  conclusive  evidence  of  syphilitic 

infection.  1  *     •  ^ 

The  effects  of  ordinary  intravenous  —  as  opposed  to  mtra- 
i„ous-  treatment  is  much  less  marked  than  in  cerebrospinal 
svphilis  Cases  with  a  marked  pleocytosis  may  show  a  very 
considerable  reduction  in  the  cell  count,  but  it  will  seldom  reach 
nomial  limits.  The  globulin  increase  is  still  more  resistant, 
and  the  Wassermann  reaction,  except  in  cases  where  there  is 
reason  to  suspect  a  large  meningeal  element,  can  rarely  be  con- 


SYPHILIS   OF   THE    NERVOUS  SYSTEM 


«I7 


i 


verted  from  a  positive  into  a  negative.  Some  of  the  cases  of 
tabes  dorsalis  and  even  of  general  paresis,  however,  trcate.l  at 
the  FJoston  Psychopathic  Hospital  by  Southard  and  Solomon 
by  intravenous  injections  only  have  shown  extraordinary  im- 
provement in  the  serology  of  their  spinal  fluids,  every  single 
pathological  feature  having  returned  to  normal  (personal  com- 
munication). 

GENERAL  PARESIS 

There  is  no  condition  in  clinical  medicine  in  which  an  ex- 
amination of  the  cerebrospinal  fluid  is  of  greater  importance 
than  in  general  paresis,  nor  one  in  which  the  findings  are  more 
constant  and  characteristic.  The  differential  diagnosis  be- 
tween general  paresis  in  the  early  stages  and  neurasthenia, 
alcoholic  insanity,  cerebrospinal  syphilis,  and  other  conditions, 
is  often  one  of  extreme  diflkulty,  and  the  help  which  the 
laboratory  is  able  to  provide  may  be  welcome  in  the  extreme. 
Absence  of  pain  on  lumbar  puncture  is  a  characteristic  feature. 
I  do  not  remember  puncturing  a  paralytic  who  complained  of 
discomfort  at  the  time  of  the  operation.  Further,  such  pa- 
tients are  singularly  immune  from  unpleasant  after-effects. 

The  pressure  may  be  normal,  but  as  a  rule  it  is  distinctly 
raised.  The  total  volume  of  fluid  is  increased,  this  being  no 
doubt  compensatory  to  the  atrophy  of  brain  tissue. 

The  fluid  is  almost  always  clear.  In  one  case,  however, 
with  a  phenomenal  cell  count  —  over  3,000  cells  per  c.  mm.— 
it  was  opalescent.     Fehling  reduction  is  prompt. 

A  cellular  increase  is  the  almo.st  universal  nile.  Should  a 
case  fail  to  show  such  an  increase  when  examined  on  several 
occasions  the  clinical  evidence  would  need  to  be  overwhelming 
before  a  diagnosis  of  general  paresis  could  be  accepted.  The 
pleocytosis.  together  with  the  other  positive  findings,  is  de- 
pendent to  some  extent  on  the  stage  of  the  disease,  and  also 
upon  the  type.  In  a  series  of  obsenations  on  asvlum  patients 
T  found  that  the  spinal  fluid  changes  were  much  more  marked 
in  the  early  stages  than  when  the  patient  had  sunk  \ntn  a  con- 
dition of  dementia  in  which  he  might  continue  to  drag  on  a 


n 
It 

»  * 


¥'i 


!) 


v 

4-' 


I 


I  I; 


118       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

miserable  existence  for  a  number  of  years.  Further,  the 
acute  type  which  rapidly  passed  through  the  various  stages 
and  ended  fatally  within  a  couple  of  years  showed  a  similar 
intensity  in  the  fluid  changes  as  compared  with  those  cases 
which  pursued  a  more  leisurely  course  during  a  numlKT  ()f 
years,  although  in  these  latter  the  cerebral  lesions  characteristic 
of  general  paralysis  were  present  at  autopsy.  In  ordinary 
cases  the  number  of  cells  averages  from  30  to  ino  per  c.mni. 
but  as  indicated  alxive  this  number  may  \)C  greatly  exceeded. 
Polymorphs  can  usually  be  found  in  small  numbers,  but  after 
a  convulsive  seizure  they  may  appear  in  such  large  numbers  as 
to  equal  the  lymphocytes. 

The  small  l>Tnphocyte  's  the  predominant  type,  but  in  .Mz- 
heimer  sections  every  v;  .iety  of  cell  known  to  occur  in  the 
fluid  may  be  found.  Of  these  the  most  important  is  the 
plasma  cell.  It  used  to  lie  thought  that  these  cells,  so  char- 
acteristic a  feature  in  sections  of  the  brain  in  this  condition, 
were  not  present  in  the  cerebrospinal  fluid,  but  the  .Mzhcimcr 
method  has  shown  that  they  are  very  constantly  present,  al- 
though only  in  small  numbers.  The  presence  of  these  cells 
in  the  spinal  fluid  is  so  characteristic  as  to  I)e  almost  pathog- 
nomonic of  the  condition,  but  they  have  also  been  fotmd  in 
tuberculous  meningitis.  Endothelial  cells.  Gittcrzellen.  and 
"  tailed  cells  "  are  also  found.  The  exact  significance  and 
diagnostic  importance  of  many  of  these  cells  is  not  known, 
but  further  studies  may  be  expected  to  throw  valuable  light 
on  this  aspect  of  the  subject. 

A  high  protein  content  is  a  very  constant  feature,  and  the 
globulin  reactions  are  positive  in  over  05  per  cent,  of  cases. 
The  total  protein  varies  from  o.i  to  0.3  per  cent,  and  the 
globulin  test  may  give  a  positive  reaction  with  a  high  dilution ; 
indeed  one  of  my  cases  gave  a  distinct  reaction  with  a  dilution 
of  T  in  i.'^.  The  protein  increase  is  most  marked  in  the  earlv 
stages,  tending  progressively  to  diminish  as  the  more  chronic 
stages  are  reached.  Tt  is  ver\'  seldom  that  the  fluid  of  an  un- 
treated case  will  give  a  positive  Wassennann  if  the  globidin 
reaction  is  not  positive. 


SYPHILIS  OF  THE   NERVOUS   SYSTEM 


119 


'I'lie  Wassermanii  reaction  is  strongly  positive  both  in  the 
l)lood  and  the  cerebrospinal  fluid  in  at  least  96  per  cent,  of 
cases;  some  workers  obtain  100  per  cent,  of  positive  results. 
It  is  very  rare  for  the  reaction  to  be  positive  in  the  serum  and 
negative  in  the  fluid.  In  very  chronic  cases  the  serum  may 
give  a  negative  reaction  while  the  fluid  still  remains  positive. 
The  reaction  in  addition  to  being  extremely  constant  is  char- 
acteristically intense.  It  will  always  be  obtained  with  0.2  c.c. 
and  often  with  the  whole  series  of  dilutions.  There  is  no 
other  condition  which  approaches  general  paresis  for  the  in- 
tensity of  the  reaction. 

It  will  thus  be  seen  tliat  in  general  paresis  the  "  four  re- 
actions "  of  Xonne  are  most  characteristically  present,  namely 
a  positive  Wassermann  reaction  in  the  blood,  cellular  increase, 
globub'n  increase,  and  a  positive  Wassermann  reaction  in  the 
.spinal  fluid.  All  four  reactions  will  be  found  in  at  least  96 
per  cent,  of  cases. 

Less  efTect  is  produced  by  treatment  on  the  condition  of  the 
spinal  fluid  that  in  any  of  the  other  nervous  manifestations  of 
syphilis.  The  pleocytosis  may  become  less  marked,  but  the 
globulin  and  Wassermann  reactions  often  resist  all  therapeutic 
efforts.  With  combined  intravenous  and  intraspinal  injections 
of  salvarsan,  however,  if  sufficiently  long  continued,  the  fluid 
may  in  many  cases  be  reduced  to  a  normal  condition. 

To  the  four  classical  reactions  of  such  proved  value  in  the 
diagnosis  of  general  paresis  must  now  be  added  a  fifth.  For 
the  colloidal  gold  reaction  of  l.ange  not  only  is  as  characteristic 
as  any  or  all  of  the  classic  four,  but  it  serves  to  differentiate 
general  paresis  from  other  syphilitic  nervous  conditions  with 
a  snrencss  which  cannot  be  claimed  for  any  of  the  other 
tests. 

The  typical  paretic  curve  has  already  been  described  in  dis- 
cussing the  reaction.  Complete  precipitation  is  obtained  in 
tlie  paretic  zone,  that  is  to  say  in  the  first  3,  4.  or  3  tubes. 
The  curve  then  drops  with  varying  degrees  of  abruptness  to 
the  ?ero  line,  in  a  manner  described  by  Kaplan  as  step-ladder. 
The  reaction  is  very  constant,  being  present  in  at  least  95  per 


li 


I.  "I 


'4 


4'' 


, 


I20       PMYSI0UX;Y   and  pathology  of  the  CERmROSPINAI     I  LUID 

cent,  of  C.1SCS.  Its  intensity  l)ears  no  dcfinitr  rclati"u  to  tlic 
amount  of  protein  in  tlic  thiid.  I  his  is  sonKuIi.il  rtuiarUaMc, 
as  tlic  test  was  ()ri},'inally  introdiuec'  with  tlic  oliject  nf  ohlaui- 
inj;  a  (|uantitative  determination  of  the  protein  present.  The 
I-:inj.je  test  closely  parallels  the  Wassennann  reaction,  hut  m  a 
few  cases  it  may  j,'ive  a  positive  result  when  the  Wassennann 
reaction  is  negative.  It  is  certainly  an  extremely  vahiai)lc  cor- 
rolH)rative  test  for  ^jeneral  paresis.  In  cases  un(krj,'ouijj  treat- 
ment it  usually  diminishes  in  intensity  if  the  other  pathological 
changes  are  clearing  up.  I>ut  sometimes  it  may  reniam  e\  en 
after  the  thud  has  l)ecome  otherwise  imnnal. 

In  talies.  cerebrospinal  syphilis,  and  congenital  syjdnii^  an 
entirely  difYerent  reaction  is  obtained  lutlier  no  reduction 
occurs,  or  a  reduction  of  varying  intensity  in  the  mill  nr  luetic 
zone.  The  resulting  curve  can  he  differentiated  at  ;;  giance 
from  that  typical  of  general  paresis.  It  is  this  power  of  dif- 
ferentiation which  gives  the  colloidal  gold  test  its  value. 

JUVENILE  GENERAL  PARESIS 

In  this  condition  the  cerebrospinal  fluid  shows  the  same 
pathological  changes  as  in  the  adult  form  of  the  disease.  The 
four  reactions  and  the  I^nge  test  are  all  positive. 

In  practice  general  paresis  has  to  be  differentiated  from  a 
number  of  clinical  conditions.  In  the  majority  of  these  the 
laboratory  e.xamination  of  the  cerebrospinal  tluid  is  of  the 
greatest  value,  and  at  once  serves  to  clinch  the  diagnosis.  The 
only  real  difficulty  lies  in  distinguishing  between  general 
parcsi.s  and  cerebrospinal  syphilis.  In  both  of  the>e  the  W'as- 
sermann  reaction  in  the  blood  is  ])ositive,  and  the  spinal  fluid 
shows  a  pleocytosis  and  a  globulin  increase.  The  Wasser- 
mann  reaction  in  the  fluid  in  general  paresis,  however,  is  al- 
ways positive,  whereas  it  is  negative  in  at  least  70  per  cent, 
of  cases  of  cerebrospinal  syphilis  with  0.2  c.c.  of  fluid.  When 
larger  (piantities  of  fluid  up  to  1.0  c.c.  or  2.0  c.c.  are  used 
the  figures  may  lie  brought  up  as  high  as  in  general  paresis, 
i'.vcn  when  a  positive  result  is  obtained  with  o.j  c.c.  of  fluid 
in  cerebrospinal  syphilis  the  reaction  is  not  so  marked  as  in 


SYI'HILIS   OF    THE    NKRVOUS   SYSTEM 


131 


parcMs.  If  f,,  tlii.>,  (liflcrciKc  i>  addcW  thi-  very  <lifftrciit  l.c- 
liavK.r  (,f  till-  c<>IIi>,|ial  gold  reaction  in  the  two  conditions, 
and  the  c<|uall\  difffrcnt  response  to  spceific  treatment,  it  will 
l)e  foiMid  that  the  information  furnished  hy  the  lalv)ratory 
will  enable  the  clinician  in  practically  every  case  to  arrive  at 
a  correct  diagnosis. 

'rile  varions  reactions  in  those  forms  of  syi)lnlis  which  af- 
fect the  nervous  system  are  >ho\vn  in  the  following  table. 
The  phis  signs  indicate  that  a  poMtive  result  is  ohtaincd  in 
nearly  every  case.  The  Wassermann  reaction  in  the  fhiiil  is 
reckoned  on  the  assumption  that  o.j  c.c.  are  used. 


Sooondary 
Sypliilis 

Wassermann  in 
blood   

+ 

\\'assennann  in 
fluid 

Pleocytosis     

("ilobiilin     

50% 

I-anpe  (paretic 
curve)     

— 

REFERENCES 

Royd,  W. :  The  cerebrospinal  fluid  in  certain  mental  conditions 
Jour.  Med.  Sc,   1912,  T.XVIIT.  p.  20,^ 

Dreyfus:  Die  Bcdcutuni,'  der  niodernen  I'ntersuchunRS  und 
Redhandlunps  methoden  fiir  die  Reurtcilunp  isolicrter  Pupillenstor- 
unpcn   nach  vorcnsjranpcncrcr  Lues.     Miinch.  nied.  Wocli.,   1012.   p. 

Fruhwald.  R.  and  Zaioziecki.  A.:  Ubcr  die  Infcctiostat  dcs 
T.iquor  cerebrospinalis  bci  Syphilis.  Berlin,  klin.  Woch.,  1917.  LIII, 
Xo.  I. 

GresTory  and  Karpas:  A  case  of  cerebral  syphilis  occurring  si.x 
months  after  the  initial  lesion.  Rev.  of  Xcurol.  and  Psvch..  May, 
'Oi.r 

Kaplan:     Serolojjy  of  Xcrvous  and  Mental  Diseases.     1914,  W.  B. 
Saunders  Co. 
I-evaditi,  C,  Marie,  A.,  and  Bankowski,  L.:    Le  treponeme  dans 


!•-.; 


i.; 


'''J 

.\  'ft 


H 


U2       PHYSIOLOGV  AND  PATHOLOGV  OF  THE  CEREnROSPINAL  FLU.D 


''asteur,  1913, 


le  cerveau  des  paralytiques  generaux.    Ann.  de  - 
AXVII,  p.  576. 

pailS't'L'h'  ''""•  ^-  '''■■     ^  ''<^-°-»"tion  of  trcponcna 

Med  r^^rivii  ri" '""  '^""'  ''^^^'•^'^-  -'''"•■•  ^^^p-- 

Nonne    M  •     Syphilis  und  Xcrvensystem,  Herl.n.   1902. 

der   Lerebrospinalflussiffkc.t,    1913,   Fischer,  Jena. 

U  lie    U.  J.  •     The  spirochetal  content  of  the  spinal  fluid  of  tabes 
general  pares,  and  cerebrospinal  syphilis.  Am.  Jour.  SypJi.is    ^J"; 

ternduril/.  {.  "'' • ''"'"'  ^^  "'^     ^"v^'vement  of  the  nervous  sys- 

1915  ls;';  i;r' "'''  °'  "^■''"'-  -  °"^-  ••''"•  ^^^^'-  -^-'- 


CHAPTER  XVI 
ORGAXIC  DISEASE  OF  THE  BRAIN 

CEREBRAL  TUMOR 

TIic  i)rcssiirc  of  tlic  cereljrospiiial  fluid  is  raised  sometimes 
t.)  siicli  an  enormous  extent  that  the  fluid  shoots  right  across 
the  bed  when  tlie  needle  is  inlnnhiced.  In  these  cases  the 
minimum  amount  of  flui.l  sliould  he  withdrawn —  not  more 
tlian  2  or  3  c.c— and  the  foot  of  the  bed  should  be  kept 
raised  for  some  time.  The  mechanism  of  the  accidents  which 
sometimes  occur  in  lumbar  puncturing  these  cases  has  al- 
ready been  discussed. 

The  cell  count  as  a  rule  is  normal,  but  mav  be  increased, 
especially  in  tumors  involvin,<r  the  meninges,  'in  one  case  of 
tumor  of  tb.  pituitary  body  there  was  a  very  marke.l 
pleocytosis.  .  ,  this  case  the  somewhat  rare  condition  of 
cerebrospinal  rhinorrh.ra  '  is  present,  for  a  communication 
existed  — owing  to  the  destructive  action  of  the  new  growth 
—  between  the  cranial  and  the  nasal  cavities,  and  whenever 
the  patient  sat  up  cerebrospinal  fluid  dripped  from  the  nose 
In  gumma  of  the  brain  a  considerable  Ivmphocvtosis  mav  be 
present. 

The  protein  content  varies  much  as  the  cell  count.  As  a 
rule  it  is  not  increased.  It  is  more  likelv  to  be  raised  if  the 
tumor  ,s  a  gumma.  In  the  pituitary  case  above  mentioned 
there  was  an  enormous  increase. 

Rehm  records  the  presence  of  cholesterin  crvstals  and  fat 
needles  m  a  case  of  cholesteatoma  of  the  base  of  the  skull 
and  I  have  found  cholesterin  ester  crystals  in  a  case  of  tumor 
of  the  optic  chiasma. 

In  echinococcus  .liseasc  of  the  brain  it  mav  be  possible  to 
demonstrate  the  presence  of  booklets  and  fragments  of  mem- 
brane in  the  spinal  fluid, 

123 


•  i.MJ   lATMOI.fK.'V    Of.    llli;   CtRliBROSl'INAL  FLUID 


CEREBRAL  ABSCESS 


.\l..ci 


1.  'I 
."  '! 

■:  •) 

»' 

.'■) 


^'ss   ..I    il,c   l,rain   may   ,,rcscnt  a  (lilT.cIt   pml.leni   in 
<^-^s.s.      11,,  .„„,,  „„,  ,,,  ,,   .,^i,,i,,^,^  ^^_^^,  ^,_^  ^^^     ^^^_ 

"iat..ns>  s.)  nuletenn.nato  tl>at  .^rcat  .liniciiltv  niav  I.c 'exper- 
ienced m  arriving  at  a  deeision.  Tl,e  spinal  niml  Inulin.s  mav 
^  1  d,m  or  „,ay  he  „,islead,„^.  They  will  not  n,islea<K  hou^. 
tN  r,  ,,  „  ,s  iK.rne  ,n  n,i„d  that  a  cerebral  al,>cess  n,av  c.exist 
-•H  a  IKT.ealy  ,„nnain„id.      Indeed  it  is  often  the  X^^ 

i.utor  in  the  diai^Miosis.  ^ 

-ll-c  chief  -lithcnhy  !ie>  in  diMin;;ni.hin^  hetueen  ahsce^s  of 

e    .ram  and  septic  ntenin.^itis.     In  the  latter  condition' the 

1^"'I   's   mm,  en,   and   presents   the   nsnal   characters   seen   in 

•"-'"."'•■s.      F,    the    hrain    ahsce.s    connnnnicates    with    the 

surface  tts  c.MUent.  u  ill  he  .H.char^ed  into  the  s„l,arachnoid 

pace,  a  pnrnlent  ,netn-n,,itis  will  resnlt.  and  there  will  he  no 

'fjrence    n,    the    cerehn.pinal    HnM    in    ,he   two   conditions. 

.1-'.  ever,  the  al.ce.s  he  deep  seated  the  spinal  Hnid  mav 

^d^'Sr"-,    ^^  ■'-  --  -^'-ympton.  of  acnte 
r  I.ra    ,rr,tat,on  and  pre..„re.  a  moderate  de^rree  of  pvrexia. 

^  I-  al  f  n,d.  the  stron..  presnmption  is  that  the  condition  is  one 

\aiue  than  a  positive  one. 

h  has  alread.v  heen  seen,  however,  that  even  in  a  deep  seated 

:    --  m  uhu-h  the  antop.y  niav  reveal  no  evidence  If  nien- 

n   .t,s  chanc...  niav  he  present  in  the  fluid  in  the  shape  of  a 

e  hilar  an,    ;,lohnlin  increase.     This  is  apparentlv  .In     to    he 

;      --..to.n,sfronMheahscesseat,sin,acertainanJ 
I't  ineniiiy-eal  irritation. 

_    The  connnone:-,  ..nrce  of  a  cerehral  ahscess  is  the  middle 
'>■•      Infer,„,„   ,„,,■  ,,,,,i,,   ,„,,,,^,  „,^,,,,,^,^   ^,^^  ^^_^^^^^^^^   ^^^^_ 

pani  and  .^ive  rise  to  an  alwccs  in  the  temporo-sphenoidal  lohe 
K  .^  miKn-Vah!.,  |,„.,.v..r.  i„  !,„u-  n,-,„v  instance,  no  meningitis 
results  rom  this  spread.  al.hon,h  the  infection  mnst  have 
traver.ed  the  subarachnoid  space.     This  immunitv  of  the  men- 


«SB_ 


ORGANIC    DISEASE   OF   THE    BRAIM  ,33 

i"g<^s  is  due  to  the  walling  off  of  the  area  of  infection  hv  ad- 
.cMon.,  u  h.ch  prov.de  an  efllcient  protection  when  tl,e  proce  s 
i.^  not  too  acute.  ' 

The  a,.Khtn.n  of  the  cerebrospinal  fluid  may  change  .luring 
the  ourse  ot  a  cerebral  abscess,  so  that  if  a  prelin^in-iry 
puncture  reveals  a  normal  ,Und  it  may  be  ucli  t.  n  ak  ! 
I  lier  exanunat.on  a  day  or  two  later.  The  following  ce 
Illustrates  this  m  a  remarkable  way.  " 

Tlie  patient   when   (irst  seen   complained  of  headache  and 

'lunness  ot  v.s.on.     Two  years  before  he  had  suffered  f"n 

p-vere  headaches  and  a  left  hennplegia  which  were  svphi   " 

"  ongm  and  which  completely  disappeared  under  aut'i  svpl  i 

1  t.c  treatntent.     The  present  attack  of  headache  and  lo      of 

n  ne  I  loT  ,  ''''  '""'•  '"'^"  "'-'--l>i"al  lluid  con' 
ta.ned  i  lo  lymphocytes  per  c.  mm.  The  evident  .liagnosis  ap- 
peared   o  be  one  of  return  of  the  syphilitic  cerebral^Ufection. 

.u     anl,-syphd,  ,c   treatment   was   without  effect.     The   si^ht 

fade.l  rapully.  the  left  am,  becan.e  paralysed,  and  the  patient 

•sank  mto  a  condition  of  coma,  which  temtinate.l  i„  a   few 

^  ays  m  death.     On  the  day  before  he  died  lumbar  puncture 

uas  agam  pertormed.  and  to  my  surprise  I   found  that  the 

'1^'"1  was  now  turbul.  and  contained  large  numbers  of  polv- 

niorphonudear   leuccvtcs.     The   chronir    .vnI,;iT  ' 

...  ,    ,  -   ^^      '  "e   cnronic   svpinhtic   con<  ition 

lud  apparently  been  replace.l  by  an  acute  suppurative  one 
A  v.s.t  to  the  autopsy  room  provided  the  explanation      In 

he  nght  motor  area  were  the  remains  of  a  svphilitic  gt.mmr- 

o  wuch  were  due  the  hemiplegia  of  two  vears  ago.  T.nd  e 
lymphocytos.s  which  .still  persisted.  In  ad.li'tion.  h-Twever  two 
acute  abscesses  were  present,  one  in  the  right  motor  area  tne 
other  m  the  occpital  lol..     The  pus  from  the  latter  had  made 

s  way  „,to  the  ventricles,  and  thence  to  the  base  of  the  brain 
through  the  locus  perforatus  po.sticus.  The  abscesses  were  the 
cause  of  the  recent  henn-plegia  an<l  the  l,>ss  of  vision  The 
change  m  the  character  of  the  spinal  Hui.l  was  due  to' a  real 
change  m  the  infection,  but  the  relationship  was  not  reco-mized 
and  an  unavailing  line  of  treatment  was  the  result 


126        PHYSIOLOGY  AND   PATHOUKiY  OF  THE  CERI-BROSPINAL  FLUID 


CEREBRAL  HEMORRHAGE 


I 


< 


M 


i 
I 


In  many  cases  of  txTcliral  haMuorrliaj^e  the  spina!  Iluid  is 
(jnitc  normal.  In  a  few  there  may  lie  a  moderate  lympho- 
cytosis and  a  slight  j^lolnilin  increase.  Should  the  arterial  dis- 
ease he  syphilitic,  the  Iluid  will  show  correspondiuj:^  chau>,as. 
aIthouf;h  it  must  he  rememhered  that  the  purely  arterial  form 
of  cerchral  .syphilis  leaves  fewer  traces  in  the  Iluid  than  any 
other  variety. 

If  the  h.Tmorrha!::je  is  near  the  surface  or  leaks  into  the  ven- 
tricles, red  blood  cell.s  will  be  found  in  the  fluid  in  lar<;e 
numbers. 

Subarachnoid  ha'morrha^e  may  thus  be  due  to  an  orijjinal 
ha'uiorrhaj^e  in  the  brain.  .\  nutch  more  frequent  cause, 
however,  is  h;emorrhajjc  from  a  menincjeal  vessel.  This  's 
usually  due  to  injury  to  the  skull,  but  may  occur  from  other 
causes.  In  one  case  thcK  was  ;i  history  of  the  jjaticnt  liftinj;: 
heavy  bo.xes,  with  the  onset  in  a  couple  of  hours  of  symptoms 
of  cerebral  compression.  The  behavior  of  the  cerebrospinal 
Iluid  in  this  case  may  be  taken  as  typical  of  the  whole  class. 
On  the  day  following  the  onset  the  fluid  was  under  moderate 
pressure,  and  jiresented  the  appearance  of  pure  blood.  On  be- 
in}T  centrifuf,'ed  a  thick  layer  of  red  cells  collected  at  the  bot- 
tom of  the  tul)e,  the  supernatant  fluid  showing  an  almost  im- 
perceptible yellowish  tinge.  A  couple  of  days  later  there  was 
still  an  abundance  of  red  cells,  but  considerable  hrcmolysis  had 
taken  place,  and  the  Iluid  was  of  a  canary  yellow  color.  At 
the  end  of  a  week  the  red  cells  had  largely  disappeared,  but 
their  place  was  taken  by  large  numbers  of  polymorphonuclear 
leucocytes,  together  with  a  small  portion  of  lymphocvtes.  It 
was  not  possible  to  follow  this  case  further,  but  in  similar 
cases  it  is  connnon  to  find  mmibers  of  large  phagocytic  cells 
showing  numerous  cell  inclusions  in  the  later  stages  of  the 
condition.  Lymphocytes  and  large  mononuclear  cells  have 
been  found  a  considerable  time  after  the  occurrence  of  the 
h.Tmorrhagc. 

Reference  may  here  be  made  to  certain  changes  which  have 


ORGANIC   DISEASE  OF   THE    BRAIN  i2J 

been  observed  in  the  brain  and  spinal  fluid  in  cases  of  shell 
shock  Ihe  bursting  of  a  large  high  explosive  shell  in  the 
mmiediate  vicinity  may  produce  neurological  phenomena  be- 
wildenng  m  their  variety,  and  sometimes  strongly  suggestine 
a  functional  basis.  It  has  been  found,  however,  that  if  the 
spinal  tlmd  of  such  cases  is  examined  shortly  after  the  injury 
blood  will  be  very  constantly  observed.  Mott  and  others  have 
further  demonstrate  that  if  such  patients  die  from  other 
uijunes  numerous  petechial  h.Tmorrhages  may  be  found  scat- 
tered throughout  the  brain  and  spinal  cord. 

CEREBRAL  THROMBOSIS 

In  thrombosis  of  the  cerebral  vessels  proper  the  spinal  fluid 
"lay  present  no  aI,normaIity.  I„  syphilitic  cases  there  will 
probably  be  a  lymphocytosis  and  a  globulin  increase  \ 
positive  Wassermann  reaction  in  the  spmal  fluid  will  settle  the 
ctioloiyy  of  the  condition. 

'_^ehm  has  (lescribed  marked  changes  in  sinus  thromWsis 
This  usually  involves  the  lateral  sinus,  most  commonly  in  in- 
flammatory conditions  of  the  middle  ear.  but  anv  of  the  sinuses 
may  be  affected  from  either  local  or  general  causes.  The 
fln.d  may  be  clear,  of  normal  pressure,  and  contain  no  ab- 
normal constituents.  On  the  other  hand  the  pressure  mav  be 
considerably  raised,  and  the  fluid  mav  be  of  a  yellow  olor 
and  contain  large  numbers  of  re<l  blood  corpuscles.  In  some 
cases  the  fluid  is  cloudy,  shows  a  marke.l  leucocvtosis"  and 
contains  large  .|.iant,ties  of  albumen.  Occasional'lv  a  def- 
inite network  of  fibrin  forms  in  the  fluid. 

ENCEPHALITIS 

Encephalitis  or  diffuse  inflammation  of  the  brain  mav  occur 
as  a  complication  in  such  conditions  as  acute  meningin's  and 
cerebra  abscess.  The  most  important  and  interesting  form  in 
which  It  occurs,  however,  is  as  encephalitis  lethargica.  a  disease 
characten.e.I  bv  lethargv.  cranial  nerve  .listurbances.  and  foci 
of  inflammation  scattered  throughout  the  brain,  more  especially 
.'n  the  mid-brain  and  medulla.     The  condition  of  the  spinal 


I  \ 

in  * 


II  if 


!    W* 


:| 


123        IMiVSIOLOGY   AM)    I'ATMOIOOY   OF   TlIU   CtRliBROSIMNAL   FLUID 

l1i,i(l  varies  j,'rcatly  in  (lifftTont  casos.  In  a  scries  of  over  40 
cases  seen  in  Winnipeg'  at  the  end  of  i<)i9  tli^'  pressure  was 
almost  invariahly  raised,  Imt  there  was  no  other  constant 
chan.!;e.  In  tlie  majority  tlie  cells  and  -;lolnilin  were  normal. 
In  a  small  proportion  there  was  a  moderate  increase  up  to 
-,n.  and  in  two  the  count  was  13-'  an.l  -'lo.  The  increase  in 
^dolmlin  was  not  i)roportionate ;  there  beinj;  never  more  than 
a  trace  present.  The  suj;ar  was  normal.  Xo  l.actcria  were 
found  in  culture. 

HYDROCEPHALUS 

The  condition  <.f  !iy<Irocei)halus  has  been  known  to  medical 
science  since  the  days  when  Hippocrates  with  a  master's  sure 
iiiML;ht  first  tai)i)ed  the  hydr.)Ce])halic  ventricle.     In  the  cen- 
turies which  have  elai)^-ed  since  then  little  or  nothing,'  has  been 
added  to  our  knowled.ijc  of  the  subject,  and  as  .Matrendie  has 
remarked,  we  merely  cloak  ,nir  i-norance  in  words  when  we 
apply  the  hij^h  soundin-  term  hydrocephalus  to  the  con.lition 
known   to  everv   layman  as  "water  on   the  brain."     It   was 
Mai;cndie  himself  who  br.t  recognize.!  that  obstruction  of  the 
aqueduct  of  Sylvius  was  followed  by  dilatation  of  the  lateral 
ventricles,  but  he  was  unable  to  explain  the  phenomenon,  as  he 
was  unaware  that  the  lluid  was  produced  in  the  lateral  ventri- 
cles.    With  increased  knowledjjc  regardin<,'  the  physioloj^y  of 
llie  lluid,  however,  and  with  some  little  insij^du  into  the  factors 
i^n.verniu!^'  its  production  and  .absorption,  there  is  hope  that  an 
underst.andint;   of    the   Cduditinii    may   yet    be  attained    which 
will  ,1,'ive  us  the  power  of  ,t,'rapi)lins  with  a  disease  th.at  has 
hitherto  ballled  the  be>t  sur,ii:ical  elTnrt. 

The  m-ist  e\hausti\e  work  on  the  subject  is  that  of  Handy 
.•uid  r.iarkfan,  who,  in  additiuu  to  cleariuLr  up  many  doubtful 
jMiint'^.  intrnduced  new  metlMik  of  inxe-ti-atidu  which  ^dve 
l)r()mi-c  i.f  bcarin-  very  fmitlul  roult^^.  They  ])ro(luced  ex- 
treme (le.t,'rces  of  hvdroceiihaUis  e\i)erimentally  by  introducin,;^ 
a  p!ed.i,Mn  nf  cottim  \\<<n]  into  the  :i'|ueiluct  nf  S\Ivitis.  'I  hoy 
were  :d-(>  able  {•>  i>n.dii((  ]c<-er  (le.D;re-s  of  hydrocephalus  by 
ligatiufr  the  vein  of  r.alen  or  the  >traight  sinus.     Ry  injecting 


ORGANIC   DISEASE   OF  THE    BRAIN 


129 


phenolsulphonephthalein  into  tlie  ventricles  and  spinal  canal 
they  were  ahle  t(j  determine  that  snnie  cases  of  liyilroceplialiis 
were  due  to  obstruction  of  the  atjueduct  ui  Sylvius,  Iiut  tlial 
in  others  the  aiiueduct  was  open  and  the  defect  appeared  to  be 
one  in  the  mechanism  of  absorption.  In  a  numl)er  of  cases 
where  a  diagnosis  was  made  of  obstruction  to  the  afjueduct 
of  Sylvius  on  the  basis  of  these  tests,  very  strikinj,'  evidence 
was  furnished  by  the  autopsy.  Thus  in  one  case  there  was 
congenital  absence  of  the  a(|ueduct. 

I'razier  suggests  that  the  condition  be  divided  into  obstmc- 
tivc,  nou-a])sorptive,  and  hy|)ersecretive  types.  In  the  first 
variety  the  obstruction  may  be  due  to  a  congenital  defect,  such 
as  absence  of  the  aqueduct  of  Sylvius,  or.  much  more  com- 
monly, to  post-intlammatory  adhesions  around  the  roof  of  the 
fourth  ventricle.  The  non-absorptive  variety  is  due  to  st)me 
interference  with  the  mechanism  of  absorption.  'Ihis  may  be 
i\uc  to  an  abnormal  condition  of  the  arachnoid  villi  or  the  cere- 
bral veins,  or  there  may  be  toxic  sul)stances  in  the  lluid  which 
prevent  its  absorption.  At  present  these  are  mere  matters  of 
conjecture,  but  recognition  of  the  variety  is  important  that 
proper  treatment  may  be  instituted. 

]'"inally,  there  is  the  third  type  in  which  there  is  hypersecre- 
tion of  the  lluid,  due  probably  to  over-activity  of  the  epithelium 
of  the  choroid  plexus,  the  result  of  the  action  of  to.xins  in 
the  blood.  Many  cases  of  meningismus  and  meningitis  serosa 
are  probably  of  this  nature.  Ouincke  describes  what  he  calls 
an  angioneurotic  condition  of  the  choroid  plexus  w''h  exces- 
sive pr()ductii)n  of  lluid.  which  he  considers  may  be  the  basis 
of  the  headaches  so  common  in  chlorosis  and  other  blood  con- 
ditions. 

Frazier  also  has  employed  the  phenolsulphonephthalein  test 
as  a  means  of  dififerentiating  between  those  different  tvpes. 
This  is  based  on  the  following  facts.  If  i  c.c.  of  the  dve  is 
injected  into  the  lateral  ventricle  it  should  appear  in  the  lluid 
withdrawn  by  lumbar  puncture  in  from  3  to  8  minutes.  Un- 
der normal  ctinditions  Go  per  cent,  of  the  dye  shouM  be  ex- 
creted in  the  urine  in  the  first  two  hours.     As  none  of  the 


•  ■ 

',* " 
't  " 

y 


■ft;. 
<4>* 


130       PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

fluid  is  absorbed  within  the  ventricles,  the  appearance  of  the 
dye  in  tlie  urine  indicates  that  there  has  boeti  a  free  escape 
fruni  the  ventricles  to  the  subarachnoid  space.  I'inally  if 
1  c.c.  of  the  dye  Ix  injected  by  lunii)ar  puncture,  nonnally 
a  trace  of  the  dye  should  apjjcar  in  the  urine  in  ten  minutes, 
and  the  entire  amount  be  excreted  in  two  hours.  In  the  ob- 
structive type  — the  so-called  internal  hydrocephalus  —  there 
will  be  a  nonnal  aI)sorption  from  the  subarachnoid  space,  but 
the  intraventricular  dye  will  appear  neither  in  the  spinal  fluid 
nor  in  the  urine.  In  the  non-absorptive  type,  on  the  other 
hand,  the  appearance  of  the  dye  in  the  urine,  whether  injected 
into  the  ventricle  or  the  spinal  canal,  will  be  greatly  delayed, 
and  the  total  amount  excreted  will  be  verj-  small. 

In  performing  the  tests  a  neutral  solution  of  the  dye  should 
be  used,  as  the  commonly  employed  slightly  alkaline  solution 
acts  as  an  irritant  to  the  brain  and  cord.  Lumbar  puncture  is 
done  and  i  c.c.  of  fluid  is  allowed  to  escape.  A  2  c.c.  svriii"-e 
containing  i  c.c.  of  neutral  phenolsulphoncplithalcin  is  then 
attached  to  the  needle  and  the  syringe  is  filled  with  spinal 
fluid.  The  diluted  dye  is  .slowly  injected,  and  the  urine  tested 
in  5  minutes  for  the  appearance  of  the  dye.  The  total  amount 
excreted  in  two  hours  is  estimated. 

Xext  day  i  c.c.  of  the  dye  is  injected  into  the  lateral  ven- 
tricle. In  infants  this  may  readily  be  done  through  the  lat- 
eral part  of  the  anterior  fontanelle.  Lumbar  puncture  is 
done,  and  the  spinal  fluid  examined  for  dye  every  five  mimites. 
The  urine  is  examined  as  above,  both  for  first  appearance  of 
the  dye  and  for  the  total  amount  excreted  in  two  hours.  In 
estimating  this  latter  quantity  the  amount  of  dye  lost  by 
lumbar  puncture  must  be  taken  into  consideration. 

The  obstructive  form  of  hydrocci)ha;;M  is  best  treated  bv 
puncture  of  the  corpus  callosum.  In  the  non-absorptive  form 
endeavors  should  be  made  to  drain  the  subarachnoid  space 
into  some  convenient  receptacle  such  as  the  pleural  cavity. 
For  the  hypersecretive  variety  Frazier  recommends  the  use  of 
thyroid  feeding,  f:  .  he  found  that  thyroid  gland  was  the  only 
substance  which  invariably  acted  as  a  depressor  to  the  choroid 


ORGANIC    DISEASE   OF   THE    BRAIN 


131 


plexus,  as  shown  by  diminution  in  the  quantity  of  cerebro- 
spinal fluid  produced. 

CONCUSSION 

Concussion  of  the  brain  or  coninioiio  cerebri  is  a  condition 
the  patholo-v  of  whicl,  is  still  far  from  thorouKhlv  understood. 
It  is  of  importance  not  so  uurIi  for  its  immc<!iate  as  for  its 
later  effects.  Months  or  even  years  after  the  orif,nnal  injury 
the  patient  may  suffer  from  headaches  of  varxin-  severity. 
Many  of  these  cases  arc  doubtless  pure  neuroses,  havinjj  their 
basis  in  the  accident  with  which  the  condition  ori-inated.  In 
other  cases,  however,  the  condition  has  a  true  organic  foun- 
dation. 

Lumbar  puncture  forms  a  valuable  means  of  differentiat- 
mg  between  these  two  classes.  The  functional  tvpe  shows  no 
abnormality,  but  i„  the  or-anic  type  there  is  invariablv 
hei;,ditened  pressure  and  an  increased  volume  of  Huid.  In  the 
early  sta-cs  the  lluid  may  be  of  a  vellowish  .^r  red  color,  and 
may  .show  an  increase  of  cells  and  -lobulin.  In  the  chronic 
staj:;e  it  is  normal  in  composition. 

The  condition  of  .shell  shock  mav  be  considered  in  this 
connection.  It  was  at  first  thouf,d,t  that  this  was  a  purely 
functional  affecli<,n,  due  to  the  extreme  shock  to  which  the 
nervous  .system  was  subjected  from  the  explosion  of  a  great 
shell  close  at  han<l.  Ravatit,  however,  exann-iied  a  scries  of 
cerebrospinal  fluids  from  such  cases,  and  in  a  considerable 
number  he  found  blood  or  a  cellular  or  globulin  increase 
Post-mortem  observations  of  Mott  and  others  have  confirmed 
the  view  that  the  condition  has  a  <lcflnite  histological  basis, 
for  in  many  of  these  cases  minute  h.xmorrhages  have  been 
demonstrated  in  the  brain  and  spinal  cord. 

OEDEMA  OF  THE  BRAIN 

Although  cerebral  a^dema  can  hardlv  be  described  as  a 
disease  in  itself,  but  rather  as  a  complication  occurring  in 
other  diseases,  vet  its  effects  are  nf  Mich  import.nnce  that  it 
deserves  separate   consideration. 


i.  • 


* 


I  ?2        PIIYSIOUH-.V   AND   I'ATMOI.OC.Y  OF  THE  CEREBROSPINAL  FLUID 

A  nu.ilcratc  degree  uf  (edema  in  most  parts  of  the  IxKly  is 
n,,t  uMiallv  i.f  imicli  imporlaiue  in  it>clt,  nor  does  it  cause 
grave  incJuvenieiue  to  tlie  patient.  In  tlie  case  oi  the  brani, 
hnucvcr.  ue  are  dealing  uilli  an  organ  conline.l  in  a  rigid 
uon-expandilile  l.ony  chamber,  and  the  effects  of  even  a  shght 
increase  in  vnhime  are  di.i)roportii)natcly  great.  A  moderate 
de-ree  .>i  .edema  is  accompanie.l  hy  lieadache  of  varying 
deljreo  uf  intciiMty,  and  marked  (cdeina  may  Ik;  followed  hy 
.tin  ni.'iv  serious  >yinptoins.  There  is  reason  to  believe  that 
one  ..1  the  iiiii)orlaiit  factors  in  the  convul>ions  and  coma  of 
uraniia  i>  cerebral  .edema,  and  in  such  purely  cerebral  al- 
fection.  a>  cerebral  tunior  and  haniorrhage  the  presence  of 
:,n  accompanying  .edema  will  greatly  aggravate  the  symptoms. 

'Ihe  c..iuliu.,ii.>  in  wliich  .edema  of  the  brain  is  liable  to 
(,ccur  are  those  with  wliich  we  are  accustomed  to  assi^ciate 
u.leina  in  .nher  part,  of  the  bo.ly.  namely  cardiac  failure. 
variou>  forms  of  an.unia,  and  renal  disease.  The  headaches 
^o  cliaracteri>tic  of  chlorosis  probably  have  their  basis  in 
cerebral  ..ilema.  The  imixirtance  of  recognizing  the  <edem- 
atou>  element  in  il.c>c  c.nditi.iiis  is  that  simple  lumbar  punc- 
line  may  allV.r.l  a  degree  of  relief  which  is  as  remarkable 
to  the  iihy-iciaii  as  it  i>  gratiixing  to  the  patient. 

rf.fi:ri:n'(  T.s 

l',,n.l.  \V.:     A  ca<o  ..i  tnni.ir  of  the  iiittiitary  txxly.     I.ancct.  iQio. 

II        ]!.       1    I  -'I. 

|'„.\,1.    \V.:     Tlio    Winnii'O-    epi.lniiic    of    cnccphaUtis    letharRica. 
four   Can.  Mol.  .\--mh-.,  pijo.  X,  Xo.  -'. 

■     Dnidv    W    |-..  an,l   I  Hack  fail,  K.  D. :     biternal  liy.lroccplialn'^ ;  an 
cx;vrinu'nt:il.  dinic.d  and  patlml-r^ical  stu.ly.     .\ni.  Jour.  His.  Child., 

i.ji).  X'lll.  1'.  4    '■  .   . 

l-i-izicT   (■    II    and  IVrt.  M.  H.:     I'actors  of  influence  in  the  oriRin 

an.l  'civoilaii.m   ..I    ihc   ccrcnro^pinal    llui.l.     Am.   jour,   of   Physiol, 

KM  \.   XXW.  p.   .V  

Irazirr,    ( '.    II.:     Type^    .'f    liyilniceiihalns  —  tlicir    diltcrentiation 

•111.1  ma'.nu-nt.     Am.   bmr.  Di-.  Cliil.l..  I'H^'.  XL  P-  ')?• 

Molt,    I'.    \V.:     Tlie   cllccts   .if   lii'.di   exjilosivcs   upon   the   central 
iK-Moiil  v.Mcin.     l.ai.cet.   19'^'.  T,  PP    33'.  44i-  a"J  ?45. 


CHAI'TER  XVII 


OKG.WIC  DISEASKS  OF  THK  Sl'lXAL  LORD 


TUMOR  OF  THE  SPINAL  CORD 

In  tumors  of  the  cord  the  cert  l)rospiiial  lluid  mav  present 
very  varvinjj  appearances,  i  may  Ik;  (|iiite  normal,  in  whicli 
case  the  examination  has  no  diajjnostic  vahie.  On  the  oilier 
hand  it  may  present  appearances  so  characteristic  tliat  a  pos- 
itive (happiosis  of  {-'■essure  on  the  cord  can  Ik;  made  on  tlic 
patholoj,Mcal  findinn^s  alone. 

'i'hese  si^'iiificant  fnidings  about  lo  he  <lescrilied  are  char- 
acteristic not  of  all  cord  tumors,  hut  of  those  producinj;  pres- 
sure on  the  cord  with  a  nsultinfj  division  of  the  canal  into  two 
segments,  a  larpe  upper  one  in  free  communication  with  llie 
remainder  of  the  subarachnoid  space,  ami  a  small  lower  one  in 
which  there  is  complete  stagnation  of  the  contained  fluid. 
The  pressure  may  he  due  to  intra-  or  exlra-medullary  tinnors 
of  the  cord,  or  to  tuhcrculous  or  malignant  disea-e  of  the 
spine.  If  an  intra-medullary  tumor  fails  to  proiluce  thi^ 
subdivision  of  the  sjjinal  canal,  the  fluid  will  fail  to  slii 
characteristic  changes. 

Two  syndromes  have  been  described  in  this  connection. 
In  iQO.^  I'roin  described  .^  fluids  whicli  showed  marked 
Nanlhochrouiia,  high  |)roicin  content,  and  sivintaneous  coagu- 
lation on  standing,  owing  to  the  large  amount  of  fibrin  pres- 
ent. In  \<)(^S  Xonne  pointed  out  that  certr-jn  cases  of  spinal 
cord  tumor  were  as'^ociatcfl  with  a  marked  nuTcase  iti  globulin 
with<nit  a  corres[)onding  increase  in  celN.  It  i^  unw  reco<:- 
nized  that  the  Xonne  syndrome  is  an  earlv  stage  of  tlie  Froin 
syndrome,  and  may  develop  ini.i  it.  It  is  pcrbajis  '<o';t  t' 
describe  the  condition  as  the  Xonni'-I'miu  sviidromo.  The 
complete  picture  loinpri'^e';  x.'uuhocbrouiia.  -spontaneous  •:-<iiv- 
ulation,   increase  of  protein,  and  absence  of  l>Tnphocytosi>. 

133 


t. 


i 


i.r; 


l.<4        I'MVSIOI.fK-.V   AND   I'ATIIOMK.V  OK  THE  I  KREnROSl'IN AI,  FLUID 

It  is  (juitc  uniK-iTssary.  Iihucwt,  that  all  ot'  tlu-.c  slumld  lie 
l)rcM'nt  in  order  that  a  (liaj^iiosis  oi'  curd  iiiini)rcs-.iiiii  .-liouid 
Ih.'  inadi".  I  he  iim^t  cliarailrri^lic  I'oaluri'  i>  (lie  ^arat  pmirin 
increase  witliout  an  iiurea^e  of  cells.  Tliis  in  it-elf,  witliout 
any  cnldration  or  siuintaiienu-,  cua^iilatiim  of  the  lliiid,  is 
siirficieiit  tor  a  positive  diajirnosis.  for  in  no  other  Unovvn  con- 
dition does  so  remarkalile  a  dissoriation  occur.  Of  the  tuo 
cases  wliidi  have  cmne  inidcr  my  own  ohservaticMi.  in  one 
there  was  a  clear  Ihiid  with  very  lari.je  protein  excess  lint  no 
pleocytosis  and  in  tiie  otiier  there  was  in  addiliin  a  tyi)ical 
NanthiH-hroniia. 

-Accordini,'  to  Mestrexat  a  yellow  coloration  of  the  sjjinal 
fluid  may  he  met  with  in  icierns.  in  meninnieal  inllammation 
with  inten-e  vascular  conta-'-tion.  in  inimite  meninjjeal  ha'tnor- 
rha':;e  of  at  least  three  days'  duration,  and  in  xanthochromia 
with  massive  coagulation. 

AlthouL^h  cliaracterisiically  ahseiit  it  liy  no  means  follows 
that  a  lymphocytosis  may  not  In-  met  with.  In  syphilitic  con- 
ditions or  where  there  is  some  inllammation  of  the  niem- 
hranes  of  the  cord  there  tnay  he  a  cellul.'ir  increase.  Init  the 
protein  will  -till  jiroIiaMv  he  fjreatlv  in  excess,  and  if  massive 
coajjulation  and  xanthochromia  arc  present  confusion  will 
not  arise. 

That  the  Xonne-Froin  .syndrome  is  not  confined  to  cases 
of  tumor  of  the  cord  is  shown  hv  the  observations,  amonj^st 
others,  of  Sicard  and  I'roin  v  ho  puhlished  a  series  of  oliserva- 
tions  on  the  spinal  fluid  in  cases  of  active  Pott's  disease.  In  all 
of  these  the  characteristic  (lissiiri;itio!i  was  present. 

Bahes  has  descril>ed  a  curious  Cindiufj  in  certain  cardiac 
cases  whom  he  classifies  as  avy-;toli(|uc  —  patients  in  whom  the 
heart  is  unaMe  to  contract  in  fu1!  s\-f(j!e.  In  lo  such  cases 
he  fouml  a  tnarked  \c11ow  coloration  <if  the  fliuM  withcMit  olher 
chanc'cs.  There  was  no  tr.ice  of  hile  in  the  lltuM.  I  fe  con- 
sidered the  condition  to  he  due  {<>  ^ta'Miation  of  the  Mood 
and  transudation  of  Mmd  pi'^uicni  ihr'iu;;li  the  \es-,el  walls. 
He  also  found  a  similar  coloration  in  snuie  acute  infections 
such  as  pneimionia  and  appendicitis,  which  he  ascribes  t'j  a 


ORGANIC    UISi:.\SKS   OF    THE    SI'IVAI,    CORO 


I.IS 


condition  of  altnonn.il  |HTnic;iI»ilit\  ut  tlic  clKiniid  pIcMis  with 
o>nsi'(|in.'nt  li.i'MinlyNi',  <»f  red  Mimd  lorpiisiii'^. 

I  Ik-  iiKTii.iiii-ni  of  the  pluiioincnoii  lias  ainacly  liciii  (Ii>- 
cii.iscil.  rill'  prevalent  view  i>  that  the  culur  is  due  to  IiKhmI 
pigment  from  ninltii)le  small  liaiMnrrliai^'es.  It  api)ears  mneli 
more  projjahle,  however,  that  the  conilitioii  is  one  of  transnda- 
tion  of  serum  into  the  spinal  cul-de-sac  owinj^  to  pressure  on 
the  meiiinj^eal  \eiious  [dexus.  The  composition  of  the  lluid 
hears  a  elo-e  re-emhlance  to  that  of  a  mechanical  etVusion  into 
such  a  sac  as  the  pleural  cavity. 

SYRINGOMYELIA 

Kaplan  >iates  that  in  this  condition  there  may  he  a  marked 
protein  increase  without  a  pleocytosis.  lie  mentions  one  case 
in  which  tliere  was  some  dej,'ree  of  xanthochromia.  'I'hese 
findings  indicative  of  cord  pressure  are  only  what  one  would 
expect.      In   four  other  cases  the  tlnid  was  normal. 

ACUTE  MYELITIS 

Very  few  oljservations  on  the  condition  of  the  spinal  fluid 
in  this  conchlion  have  been  recorded.  In  one  case  of  typical 
transverse  myelitis  uniler  my  oh-ervation  there  :i])peared  to 
Ik  a  very  small  amount  of  lluid  present,  although  punctures 
were  made  on  several  occasions.  The  Huid  ])resenteil  no  other 
abnormality.  .\  second  case  gave  a  very  marked  globulin 
reaction,  with  ,v^  I'clls  per  c.  mm.  'ihe  Wassermann  reaction 
was  negative.  In  lM)ih  of  these  cases  the  Ihiid  was  sterile. 
Rehm  describes  similar  findings  in  one  case. 

ACUTE  ANTERIOR  POLIOMYELITIS 

Descriptions  of  the  spinal  Ihiid  in  poliomyelitis  anterior 
acuta  which  have  appeared  in  the  past  liavc  varied  in  a  some- 
wdiat  surprising  degree.  One  of  the  chief  reasons  for  the 
divergence  of  opinion  has  probably  Ir'cu  the  dilTerent  stages 
at  which  the  cases  have  been  examined,  for  the  condition  of 
the  fluid,  changes  verv  r.npidlv  .is  the  (lisen-c  nd'-  ano"-.  The 
recent  .American  epidemics  have  offered  unrivaled  opportuni- 


1^6      iMivsinior.Y  anii  ivATMor.or.v  of  tiif  cnRrnRosriNAi.  fluid 


I 


^■H; 


I 


tii'^  f'  ■!■  itnc-ti,i;atin<,'  the  disease  in  every  sl:ii,a>.  and  a  very  con- 
si(Kr;iI)le  eMeii-ion  of  our  knn\vle(lt;c  of  the  Mihjeet  lias  been 
the  re-iiU, 

•|  he  lluiil  i>  Usually  under  distinctly  increased  pressure. 
The  ])resMn-e  may,  however,  be  normal.  It  is  clear,  and  may 
show  a  i^ood  liliriu  network  tm  standin^^  in  rare  eases  it  may 
lie  slit;htly  cloudy. 

The  cellular  chan-es  vary  with  the  sta!.:e  of  the  disease, 
in  the  earliest  staj^e,  that  is  to  say  before  the  onset  of  paralysis, 
there  is  Usually  a  hi,y;h  cell  count,  consistinj^  of  ivilyniorpho- 
nuclear  cells  and  lympliocytes  in  varyinjj  proixirtions.  The 
i:trlier  the  staije  the  iiii^lier  is  the  ])ercenta.ue  of  polymorphs, 
-  Inch  in  sonic  cases  may  reach  to  So  or  ()o.  Cases  with  tnrliid 
ll'-id  i::'\\v  a  very  hitrh  polymorph  count.  Larj^e  mononuclear 
or  endoihelial  cells  are  sometimes  present  in  considerable 
numbers.  ,!  lindins  always  snj,".ie<tive  of  jioliomyelitis.  In  the 
prodromal  s!;i;;v  Tcabody,  wlio-e  work  on  poliomyelitis  is  the 
most  thorouiih  and  v.duable  contribution  to  the  subject  which 
\'e  posse-s,  f.nind  that  tiie  lowest  cell  count  was  _^],  the  hi,L,di- 
ist  i<)S(>.  ii.itien  has  ].oiute<l  out  that  cases  with  meninijeal 
sMiipionis  L;i\e  the  l:irj;est  cell  counts. 

As  the  (li-ia<e  ])roi;ressos  the  cell  count  rapiilly  falls,  so 
b\  the  time  that  i)ar:dytic  symptoms  are  well  developed  —  at 
which  time  the  tluid  is  most  likely  to  be  examined  —  the 
|ileoc\tosis  may  be  moderate  or  only  very  sli;^lit.  A  coinci- 
drui  chan;;c  in  the  t\pe  of  cell  takes  place,  the  polymorphs 
beiuL;  alnio-i  entirely  replaced  by  lymphocytes.  P.y  the  end 
of  the  third  week  the  cell  count  may  have  returned  to  normal. 
A  globulin  increase  is  present  which  is  in  inverse  ratio  to 
the  incrcai^e  in  cells.  In  the  early  staii^es  it  is  slij^ht,  but  in- 
creases with  the  progress  of  the  disease,  until  it  reaches  a 
niaximiun  b\  the  third  or  fourth  week.  In  no  case,  however. 
does  the  incrcisr  become  excessive.  It  is  almost  always  l<-ss 
th.in  that  fomid  in  tuberculous  meningitis,  tlie  condition  wliich 
i.-.ost  resembles  poliomyelitis  as  ref,'ards  tlic  condition  of  the 
cen-brospin.al  llnid. 

lostphine     N'eal    lias    described    two    rare    occurrences 


m 


ORGANIC   DISEASES  OF   THE   Sl'INAI-   CORD 


IJ7 


poliomyelitis,  nanie'v  (rue  h;eniorrlia{,'e  in  tlie  tltiid  ami  the  ex- 
istence of  the  I'Y  syndrome.  These  pmhalily  indicate  a 
very  virulent  and  .n  infection. 

The  lluid  <;ives  a  .ell  marked  I'ehlint;  reduction.  This  is  a 
point  of  very  considerahle  importance  in  differential  di.if^nosis, 
for  the  menin<4itic  affections  with  which  poliomyelitis  is  most 
likely  to  he  confused  sliow  a  diminution  in  f,dncose  wln'ch  is 
often  very  characteristic.  Wollstein  ami  other  oI)servers  have 
investif,'ated  the  (|uestion  as  to  whctlier  specific  antiltodics  can 
he  demonstrated  in  the  lluid.  hut  in  no  case  has  any  trace  of 
such  antilMidies  heeii  found. 

.\n  importain  recent  contrihntion  to  the  suliject  is  that  of 
I'elton  and  Maxey  on  the  colioid.al  },'iild  re;iclii)U  in  the  cere- 
hrospinal  fluid.  These  observers  have  found  that  the  fluid 
j,'ave  a  very  constaiU  reduction  in  the  sec(Mid  or  luetic  zone,  that 
is  to  -iay  in  dilutions  of  from  i  in  40  to  i  in  ifVi.  '{"ho  reaction 
is  most  marked  in  the  first  week.  In  the  --ccond  and  third 
weeks  it  shows  some  tendency  to  weaken,  hut  in  manv  cases 
is  still  well  marked,  .\fter  the  fourth  week  it  diminishes  and 
finally  disappears. 

Fn  reviewing:  our  knowledjje  of  the  chancres  in  the  cerehro- 
spinal  fluid  in  acute  poliomyelitis  it  is  evident  that  there  is  no 
one  pathofjnomonic  feature  comparahle  with  the  presence  of 
tiie  nicninpjococcus  or  the  \\';issermann  reaction.  The  chanties 
can  in  no  sense  he  descrihed  as  specific.  .\nd  vet  it  would  he 
a  .t,'reat  mistake  to  think  that  an  examin.ition  of  the  fluid  is 
not  of  innnense  value  in  the  practical  task  of  arrivinc^  at  a 
di.'iijnnsis.  There  is  a  modern  tendcncv  to  demand  too  nnich 
from  the  laboratory,  .\ftcr  all.  in  a  lari,^-  nnmher  01  cases 
ialxiratory  results  do  not  give  information  which  is  absolutely 
specific,  but  merely  afTord  an  indication  to  the  clinician  which 
enables  Inm  to  use  his  powers  of  discrimination  and  judi^ment 
in  arriving;  at  a  correct  di.i-^riiosis.  .\  hiorh  Icucocvtosis  in  the 
blood  may  be  met  with  in  an  immense  variety  of  coivlilions.  but 
that  fact  does  not  lessen  its  value  as  a  means  of  dilTerenliatin-,' 
I)etween  colic  and  acute  appendicitis. 

Acute  poliomyelitis  has  to  be  differentiated  from  meningitic 


I     I 


I  ?8        PMYSIOI.OOV  AND  I'ATIIOI.OCY  OF  THK  CKREBROSPINAL  FLUID 


K'. 


fan 

i5:l 


1'- 


and  n(in-nieninp;itic  conditions.  Tlic  early  i)rodroinal  sta,e;c 
before  the  onset  of  tlic  paralysis  is  the  time  when  it  is  most 
important  to  make  a  correct  diajjnosis.  At  this  >ta,t;;e  the  dis- 
ease may  hear  a  c!o<e  re^emhlance  to  a  numher  of  febrile  con- 
ditions, in  which,  however,  there  is  ahsohitely  no  involvement 
of  the  central  nervous  s\stem.  The  ivj^c  of  the  patient,  the 
mode  of  on-et,  or  still  more  the  iirevalenre  at  the  time  of  an 
epidemic  of  poliomyelitis  may  suir.i^'est  to  the  ])hy^ician  the  jxis- 
sihility  of  the  disease.  A  Inmh.ir  puncture  will  at  once  settle 
the  (|uesti(iu,  for  the  non-menin.i,Mtic  affection  will  show  a 
normal  tluid,  \vhcrca■^  in  eviTy  case  of  poliomyelitis  at  this 
earlv  stacre  there  will  he  patholi'.;:^ical  chanties  ])rcsent. 

The  differentiatiou  K'twecn  poliomyelitis  and  acute  men- 
inj^itis  is.  however,  a  much  more  difficult  task,  in  so  far  at 
least  as  the  condition  of  the  cerehrospinal  tluid  is  concerned. 
The  mo-t  valuable  -uv^k-  point  is  the  presence  in  meningi- 
tis (if  the  cau-ative  or-ani-in.  The  mcTiinijococcus.  pnen- 
mococcus.  streiitocorcu-,  or  tubercle  bacilhis  can  usually  be 
demonstrated  to  the  exclu-'cn  of  p  linmyelitis.  The-e  organ- 
isms, however,  cannot  always  be  fotuid.  In  such  cases  the 
general  character  of  the  Ihiid  mu-t  be  taken  into  considera- 
tion. In  meninj:[itis  due  to  the  pyojrenic  orf^anisms  the  fluid 
is  aliu'i-t  alwavs  more  or  le<s  turbid  or  purulent,  and  the  cell 
count  an<l  protein  incrca-e  are  \ery  much  hii^her  than  in 
poliomveliti-.  The  proportion  of  ]>olymorphs  is  always  very 
hii^h.  which  i-^  never  the  ra<e  in  poliomyelitis  after  the  first  two 
or  three  ila\<.  The  I'ehlini:  reducing;-  power  of  the  fluid  is 
commonlv  decreased  or  entirely  lo^t  in  purulent  meninj:;itis. 
whereas  it  is  unaff-cted  in  poliomyelitis. 

The  diflu-ulty  of  differentiation  is  perhaps  ^^reatcst  in  the 
ca-e  of  tnbercidoU';  menint^iti--.  on  accoimt  of  t!ie  insidious 
nature  of  the  on-H-t.  the  frequent  difficulty  of  detcctini;  the 
tubercle  bacillu-,  and  the  <imilaritv  between  the  fluids  in  the 
two  cniulitioiK.  In  tubcrctilous  meiiintjitis  the  pressure  is 
likelv  to  be  hii,dier,  the  id.  !>nlin  reaction  to  be  more  marked 
in  the  earlv  staijes,  and  the  Fehlinj,'  reducinu:  power  to  be 
diminished.     .\  considerable  nnml)er  of  polymorphs  after  the 


ORGANIC    DISEASES   OF   THE    SPINAL   CORD 


139 


tliircl  or  fourth  day  suggests  meningitis.  The  presence  of 
endothelial  or  large  mononuclear  cells  in  appreciable  nuinl)ers, 
on  the  other  hand,  is  fairly  strong  evidence,  according  to 
Abramson,  of  poliomyelitis  as  these  cells  a.c  rarely  met  with 
in  tul)erculous  meningitis. 

The  colloidal  gold  test  usually  gives  a  well  marked  reaction 
in  all  forms  of  meningitis  in  Zone  3,  that  is  to  say,  with  di- 
lutions higher  than  1-160.  In  poliomyelitis  on  the  other  hand, 
the  reaction  (Kcurs  in  Zone  2  with  dilutions  I)etween  1-40  and 
I -160.  Tuberculous  meningitis  is  again  likely  to  prove  the 
greatest  stumbling  bl.x'k,  for  in  this  condition  the  maximum 
change  tends  to  occur  nearer  the  second  zone  than  in  the  other 
forms  of  meningitis.  In  a  series  of  comparative  tests  carried 
out  by  Jeans  and  Johnston,  however,  the  poliomyelitis  fluids 
gave  a  re.'iction  with  distinctly  lower  dilutions  than  did  those 
from  tul)erculous  meningitis. 

It  will  be  seen  that  although  there  is  no  single  point  in  the 
chemical  and  cystologicnl  examination  of  the  fluid  of  the  same 
diagnostic  value  as  the  discovery  of  the  tubercle  bacillus,  yet 
a  reasoned  consideration  of  the  various  facts  disclosed  will 
usually  enable  the  physici.in  to  arrive  at  a  correct  conclusion. 
It  is  in  the  early  preparalytic  stage  that  the  clinical  signs  are 
indeterminate,  and  fortunatelv  this  is  the  stage  in  which  the 
laboratory  evidence  is  most  characteristic  and  convincing. 
I'p  to  the  present  it  has  not  been  possible  to  base  the  prognosis 
on  the  condition  of  the  cerebrospinal  fluid,  for  there  innv  be 
no  (lifTerence  between  the  fluid  of  the  cases  which  are  going 
to  terminate  fatally  and  those  which  will  make  a  good  re- 
covery. 

The  bacteriology  of  poliomyelitis  is  still  in  a  verv  unsettled 
state,  and  it  is  impossible  as  yet  to  draw  any  definite  con- 
clusions from  the  work  which  has  been  done.  Two  main 
views  have  been  adv.anced.  Flexner  .nnd  his  ccvworkers  at 
the  Rockefeller  Tn^tittite  bold  that  the  "globoid  bodies" 
which  thev  have  isolated  from  the  brain  and  cord  of  cases  of 
poliomyelitis  are  the  causal  agent  of  the  disease.  This  or- 
ganism has  l)een  isolated  in  culture,  and  animal  inoculations 


■'  !| 


I40        PIIVSIOI.OGY   AND   rATIlOl.or.V   OV   Tin-    ChRi;ilR()SPI\AL   FLUID 


I /.I 


f 


^.1 


f« 


f 


have  rcpnidiicc'd  in  niDiikey-^  Ir-ions  wliicli  arc  said  to  In."  char- 
acteristic (if  the  coiKhtidii. 

Malhers.  I\(»enin\,  Xa/uin  and  Iltr/cjj,  and  otliers  Iiavo 
isdl.ited  a  strt'ptocdccu^  from  tlie  central  neiviuis  systcin  whicli, 
according;  to  them,  is  capable  of  repnxhicint;  the  (hsease  in 
monkeys.  Xazum  descril)ed  the  presence  of  this  or<:janism 
in  tile  cereliro-iiinal  ihiid  <>f  ca-es  of  jmliomyelitis.  The  most 
recent  work  of  KiKcnow  and  Towne  offers  a  sn,t,'.i;estcd  expla- 
nation of  the  differences  in  the  re>nlt>  of  the  two  sets  of 
wcirlvcrs.  The  streptncncci  isnlated  from  the  spinal  cord  main- 
tain the  form  of  diplncocci  under  ordinary  aerobic  conditions. 
\\  itii  a  medium  cnntaiuin^  a-citic  lluid  and  fre-h  sterile  tissue, 
liowever,  tliev  jjrachially  dimini-.h  in  ^i;<e  by  transverse  fission, 
and  in  tlie  course  of  ten  da\  -  a  p'ire  i,n-ii\vtli  of  i^dobnid  bodies 
inav  be  obtained.  Ro-cimw  and  Towne  are  of  the  opinion 
that  the  ijlolxiid  bodies  of  t'le  Knckefeller  Instiiute  workers 
are  in  all  cases  the  result  oi  the  brcakiut,'  dnwii  of  ]:\r'^c  dip- 
lococci.  ^b1re  cannot  lie  '•aid  on  the  subject  until  further 
work  has  confirmed  or  di<pro\eil  the  resiilts  of  tlie  difTerent 
investicfators. 

SUBACUTE  COMBINED  DEGENERATION 

\'erv  ivw  observations  on  t'le  cerebrospinal  lluid  in  this 
interestinp;  condition  are  on  record.  I  have  only  had  the 
ol>pi»rtunitv  of  examinin:^  two  case-.  The  blood  and  neuro- 
loi,dcal  pictures  were  ipiite  typical,  but  the  sjjinal  lluid  sliowcd 
little  chanjje.  There  was  a  very  -liLrht  increase  <if  <rlobuliu, 
but  the  cell  count  was  normal.  I\;iplan.  however,  describes 
three  cases  in  wliich  the  chantjes  resembled  those  seen  in  com- 
pression of  the  cord  —  very  marked  nlol)ulin  increase  with 
no  ploocytosis. 

Cases  of  pernicious  ana-niia  with  cord  chaiiii^es  which  often 
bear  so  clo^e  a  re-cmbl.uicc  to  -ub;u'ute  combined  desi^fenera- 
tion  that  it  is  difTicult  to  know  where  to  ilmw  the  line  of  dis- 
liuction,  present  a  perfectK  normal  nuiij.  That  is  to  sav. 
our  present  methods  fail  to  detect  .any  abnormality.  It  is  al- 
niost  inconceivable,  however,  that  in  a  condition  where  toxins 


ORGANIC    DISrASnS   OF    TMF    SnVAI,   CORD 


141 


must  certainly  Ix;  acting  upon  tlio  cord  the  lluid  which  I)atlies 
tlie  cord  is  in  reality  iiomial. 

MULTIPLE  SCLEROSIS 

In  a  series  of  iS  cases  whicli  I  examined  no  constant  pathog- 
nomonic chanj^^e  was  found.  The  lluid  was  clear  and  under 
normal  pressure.  In  ahont  a  quarter  of  tlie  cases  it  showed 
no  change.  In  most  of  the  cases,  liowever,  there  was  a  shght 
to  moderate  lymphocytosis,  never  exceeding  30  cells  per  c.  mtn. 
The  globulin  showed  a  slight  increase,  but  to  a  somewhat 
lesser  extent.  .Multiple  .sclerosis  is  such  a  characteristically 
toxic  disease  that  it  is  desirable  that  inoculation  and  other 
experiments  should  be  performed  in  as  many  cases  as  pos- 
sible, and  at  dilTcrent  sta.ij^cs  of  the  disease.  P.ullock  .suc- 
ceeded in  producing  suggestive  lesions  in  a  rabbit  by  the  in- 
jection of  cerel)rosi)inal  lluid  from  a  case  of  nuiltiple  sclerosis. 

HERPES  ZOSTER 

The  pathological  basis  of  herpes  zoster  bears  a  very  clo.se 
resemblance  to  that  of  anterior  poliomyelitis,  and  this  rela- 
tionship is  rellected  in  the  condition  of  the  cerebrospinal  fluid. 
In  true  her[)es  zoster  and  in  herpes  due  to  inflammation  of  the 
ganglia  on  the  cranial  nerves  there  is  a  well  marked  cellular 
increase,  the  average  ninnbcr  of  cells  being  as  a  rule  alxjut 
50  per  c.  mm.  'ihe  cells  are  mainly  small  lympluKytes,  but 
in  .some  cases  a  o)nsiderable  number  of  large  lymphcx'vtes  are 
found.  The  pleocytosis  m.iv  last  for  several  weeks  after  the 
herpetic  eruption  has  completely  disappeared.  The  globulin 
may  show  a  slight  increa.se  but  the  fluid  in  other  respects 
appears  to  be  normal. 

REFF.RF.NTES 

.XnicisS.  H.  I..:  Tlio  cultivation  and  iniinunologic  reactions  of  the 
fjlohoid  IkkIIcs  in  iioliomyelitis.  Jotir.  Fxper.  Med.,  1917,  XXV,  p. 
5-1  > 

.\hramsnn.  TI.  I,.:  The  spin.-il  fluid  in  poliomyelitis  and  its  difTer- 
cnfi.Ttion  from  fluids  of  oilit-r  infection.;.  Am.  Jour.  Dis.  Child. 
")'>  P-  344- 


142        PHVSIOLOCY  AND   PATIIOI.OCY  OF  THE  CbREBROSlMNAL  FLUID 


j"! 


tv.l 


if 


in     tfti 


I?al)cs:  La  xaniliochrDinie  <lii  li(|iii(k'  ci'plialo-racliidicii  clicz  Ics 
asy>toli(jiics.     Kciitl.   Soc.  do  liiol.    i')' }•   lAWI.  p.  ,v^. 

ILiliCs:  I. a  xaiilliuclirumio  ilu  liijuiilo  cojilialo  racliidicii  dans 
d'aiilics  maladies  (\in:  Ics  licmorrajjics  ccrcbralos,  Ics  alTcctions  dii 
lu'vraxc.s  ct  I'ictcn'.  (.'Diiip.  rend.  Scic.  dc  Iiinl.  1914,  I-XWI,  p. 
671. 

Hattcn.  F.  ("■, :  Acute  poliumvclitis.  I.ii.iilcian  Lectures,  Lancet, 
I'lif).  I,  p.  '^'i  I. 

Mronicr,  k.  S. :  I  he  syndronus  nf  coai;tdatioii  massive  ct 
xantlioclnoniie  (icciinini;  in  a  case  (if  tiil)erculi)sis  of  the  cervical 
spine,     .\nier.  JDur.  Med.  ."^c.   H)if),  t'l.L  ]).  ,^78. 

l'"clt"ii,  L.  I),  and  Ma\(.v.  K.  I".;  Tlie  colloidal  Rold  reaction  of 
the  ccreliriKpinal  llui!  11  acme  poliomyelitis.  Jour.  .\ni.  Me<l.  Assoc, 
1917,   LWllI.  p.  75-'. 

I'lexner,  S.  and  .\nt;uclii.  If.:  I'.xperinients  on  tlu-  cultivation  of 
llie  niicroiiri^ini  m  can^ini;  t  pidcniic  ])oliomyelitis.  Jour.  Lx[)cr. 
Med.,   I9t,^.   Willi,  p.  4r,i. 

I  tis,  I'  (".  and  jMluiston.  M.  I\.:  The  cerehrospinal  fluid  in 
pi  .mytlilis  with  spicial  reference  to  the  Lanj^e  reaction.  ,\nKT. 
Jtnr.  D'      Child..  11)17.  XIII.  \).  j,V) 

Kapl  ^<  roloiry    nf    Xervmis   ,r;d    Mental    Diseases. 

Mat'       -.     ( 1. :     Suinc     liacteriolos^ic      ohservatinns     on     epidemic 
poiinrr        fis.     Jour.    \  ii    Meil.  .\v-oc  .  li>l('),  I.X\()(),  j).  1019.     Jour. 
1917.  XX.  p.  I    ,; 
H. :     l.ihoratorv    .iui~    in    the   diaL^nosis   of   poliomyelitis. 
!  ediatries.   191^),   XXXIII,  p.    ;()5. 
J.    W        Ii,hterio1i.'.ric    findinjj;s    in   ccrclirnspinal    fluid    in 
is.     J    —    Am.  Mill    .\<<(ic.,  \()iC),  LX\'Il.  p.  1437. 
F.   \  The  cercl'riis[)ina1   fluid  in  ])olioinyelitis.     Jour. 

anil      'ental   Di-  asts,   I'eh.    i()i7. 

F".  '^rajicr.  <  I.,  and  l>iH-liez,  A.  R.:     .\  clinical  study 

acu  c    polji         ;itis.     .Monoi,'raphs    of    the    Rockefeller    Institute, 
0.  4.     -  2. 

Rose    <■•  '  .  and  Wheeler,  CI.  W. :     The  etiolofjy  of  epidemic 

jiolioni   eliti        'our.     .\m.    Med.   .Assoc,    1916,  LX\TT,   p.    I20j. 

Rosenow.  ..  1  .  and  Townc,  F.  I'.:  Bacteriolotjical  ohservations  in 
experimental  poliomyelitis  f)f  monkeys.  Tour.  Meil.  Research,  191 7, 
XXXVI,  p.  175. 

Sicard  and  Froin :  Dissociation  allmminncytolofjiipie  an  cours 
lies  compressions  rachidiennes.     IVesse  med.,  1914.  XX.  p.  1013. 

W'ollstein.  M, :  .\  I1ioloj.jic.1l  stud\  of  the  cerehrospinal  fluid  in 
anterior  poliomyelitis.     Jour.  Fxper.  Med.,  }<)f>X,  X.  p.  476. 


In 

•  r' 

A 

11/ 

I" 

iim 

. 'ea- 

.  f 

Xi 

Peai 

CHAPTER  X\  III 

MEXTAL  DISEASES 

The  blood  shows  so  many  changes  in  various  patliological 
conditions  affecting  the  body  that  it  might  lie  confidently  sup- 
posed that  the  cerebrospinal  fluid  which  bathes  the  inmost 
recesses  of  the  brain  would  show  similar  changes  in  mental 
disease.  And  yet.  with  the  exception  of  those  forms  of  in- 
sanity due  to  syphilis,  the  results  have  been  distinctly  disap- 
pointing. This  is  all  the  more  remarkable  because  in  some 
of  the  acute  psychoses  the  evidence  of  an  acute  irritant  l)eing 
at  work  is  in  many  cases  very  striking.  The  temperature  is 
raised,  the  tongue  coated,  and  the  blood  shows  in  many  cases 
a  well  marked  leucocytosis.  I'nder  these  circumstances  it 
might  be  supposed  tliat,  as  the  most  striking  symptoms  are 
those  indicative  of  the  action  of  an  irritant  on  the  brain,  some 
corresponding  change  would  be  found  in  the  fluid  which  sub- 
serves the  function  of  the  lymph  of  the  brain. 

MANIC-DEPRESSIVE  INSANITY 

Tn  a  long  series  of  cases  of  manic-depressive  insanity.  I 
uniformly  failed  to  find  any  change  in  the  spinal  fluid,  even 
during  attacks  of  tlie  greatest  excitement.  Other  workers 
have  obtained  similar  results.  I  cannot  but  feel  that  the  ex- 
planation of  these  negative  results  lies  in  the  coarseness  of 
the  me: hods  at  our  disposal.  If  there  is  not  a  cellular  or  a 
globulin  increase  we  conclude  that  the  fliu"d  is  normal.  The 
future,  however,  is  certain  to  give  us  methods  of  greater  re- 
finement, aufl  when  these  arc  employed  it  is  more  than  likely 
that  important  cliruige^  will  bo  found  in  the  spinal  fluid  in  the 
toxic  psychoses. 


143 


144        I'UVSIOLOGY  AND  I'ATMOLIXJY  OF  THE  CEREBROSI'INAL  FLUID 


K. 


r 


I 


EPILEPSY 

I'.pilcpsv  is  oiiijuf  tiiose  convenient  all-cnil)raciii}j  terms  in 
wliich  medicine  .still  alHinntls,  which  can  Ik;  made  to  iiicUule 
an  iniletinitc  number  of  (liftereiit  conditions.  It  is  only  nat- 
ural, therefore,  that  .some  difference  of  oi)inion  .should  exist 
conccrniufj  the  condition  of  the  cerebrospinal  lluid.  A 
inimher  of  cases  of  epileptic  convulsions  are  undouhtcdly 
syphilitic.  The  majority  of  cases,  however,  must  still  be 
classed  as  idiop.ithic.  in  these  it  is  the  rule  to  tind  no  chanjjes 
in  the  spinal  Ihiid.  In  five  such  cases,  however,  I  fi)und  a 
moderate  lymphocytosis,  ran<,nn,i,'  from  twenty  to  forty,  to- 
ijethcr  with  a  corresi)ondint,'  increase  in  };lol>ulin.  0\k  of 
these  cases  was  sufticicntly  intercstini,'  to  merit  a  brief  de- 
scription. 'Die  patient  was  a  man  of  fifty-three  years,  who 
was  a<!mittcd  in  a  restless  excited  condition,  with  marked 
delusions  and  hallucinations.  His  cerebrospinal  lluid  on  ad- 
mission showed  no  increa-e  in  cells,  and  those  present  were 
all  small  lymphocytes.  He  -cltlcd  down  and  bec.ime  ijuiet 
and  ratic^nal.  Six  mouths  Liter  lie  had  a  -evere  ejiileptic  fit 
anil  became  excited,  with  \i\id  \  isnal  ;uid  au'litorv  hallucina- 
tions. The  cerebrosi)inal  lliiid  was  examined  ;ind  found  to 
contain  .V)  cells  of  which  '>S  jicr  cent,  were  small  lymphocytes 
and  3_'  per  cent.  l;iriL;e  lymplioc}  tes.  The  lluid  was  examined 
on  five  succe-sive  days,  and  ca  -li  time  time  a  marked  lympho- 
cvlosis  was  present,  the  minilier  on  tlie  Last  occasion  bein.q 
80.  Till-  most  probable  exp!;niatinn  i^  tli.il  both  the  fit  and 
the  Ivmpliocvto-is  had  ;i  conniii'ii  inxic  oricrin. 


DEMENTIA  PR.ffi:COX 


I 


In  (knu'iiti.-i  iirircov  tin-  -pinri!  Ib'i'l  i-^  m^t  sn)!ii()-ed  to  --how 
liatliM|(i<^'ii-;il  clinni'cs,  :\ri]  ccrl.-nn''-  in  tlv  I:a!;Uoiiic  and 
paranoid  forms  tbi-  i<  n-inlly  tlu-  v:\'V.  In  10  rascs  of  the 
bcbe])bn'iiic  Ivih-,  I'mwc -r.  tbcn'  v  a-  ,-i  nKtrkcd  lymnlmcytosis 
toyctbcr  with  "iiu'  ;;liibnliii  itHTci-c.  'Ilu'-c  ra-cs  were 
mostlv  viaiii','-  ;idn!t^  who  li.-ul  -link  into  a  dull,  pble^matic, 
lethargic  condition  in  which  tlic  cliief  fenruri^  was  an  almost 


MENTAL   DISEASES 


145 


entire  loss  to  emotional  response.  They  knew  neither  joy  nor 
grief,  and  all  enujtional  contact  with  the  outer  world  seemed 
to  be  severed.  These  cases  were  e.xamined  on  several  oc- 
casions, and  each  time  the  cell  count  was  above  normal. 

ALCOHOLISM 

In  chronic  alcc^holic  insanity  the  fluid  is  quite  normal,  a 
point  of  },rriat  value  in  the  dilTcrentiation  from  f,a-'it'ral 
paresi.s.  Alcoholic  neuritis  also  |,rivcs  a  normal  fluid,  in 
marked  distinction  to  tal)cs  dor.alis,  with  which  it  mav  some- 
times be  confused,  in  acute  alcoholism  Schottmiillcr  and 
Schunim  have  demonstrated  the  presence  of  alcohol  in  the 
.'ipin.d  fluid  by  means  of  the  iodoform  test.  .Xcetone  and 
diacctic  acid  have  been  described  as  nccurrinj,'  in  the  fluid  in 
delirium  tremens. 


IDIOCY  AND  IMBECILITY 

The  application  of  the  \\:i>sermaun  test  to  the  blood  and 
spuial  fluid  in  these  conditions  has  shown  that  a  considerable 
proportion  are  syphilitic  in  ori<;in.  Such  cases  .show  the 
usual  syi)Iiilitic  cliau-vs  in  the  spinal  fluid.  Xon-syphilitic 
cases  i)resent  an  abM.lntcly  nornird  fluid. 

Other  forms  of  lui'iital  (b^case.  as  far  as  is  known,  present 
no  abnormalities  in  the  sjjinal  fluid. 

RErF.REXCES 

Hny.!.  W. :  Tin-  c-crchr,>-!iiM,i]  HiiiM  in  ccrt.iii,  mental  conditions 
Jour.  Mental  .Sc.  1912,  I. XVIII.  p.  203. 

.•^choltniiilKT  nn<l  .^clninim:  .\acliwiis  von  .\lk(,liol  in  dor  Snin.il- 
nns-ij,'kcit   von  Saufcrn.      Wiudloi;.  Ccntralhlatt,  .Nn.irnst,   1912. 


LllAl'TLK  XIX 


GLXI-IKAL  IJISI-ASKS 


, 


;ii 


DIABETES 

In  (lialK'tcs  iiitllitiis  the  su};ar  coiitcut  of  tlic  spinal  tluid 
closely  parallels  that  of  the  hlooil.  It  thus  ditfers.  as  Hop- 
kins has  pointed  out,  from  the  condition  found  in  acute  in- 
fectious hyperglyc;cinia  without  any  accompanying  increase 
in  the  cerebrospinal  ^ugar.  In  diabetic  coma  the  increase 
is  usually  very  marked  and  as  nuuh  as  '1.3  per  cent,  of  glucose 
may  he  found  in  tiic  llnid.  A  very  high  sutjar  content  is  of 
great  diagnostic  and  prognostic  iniportance.  it  is  not  an  in- 
variable rule,  however,  liiat  ca>es  in  which  coma  is  threat- 
ened slKHtld  show  thi>  great  incnasc  in  sugar  and  its  absence 
is  not  sufficient  evidence  for  a  negative  diagnosis,  although  it 
would  be  one  point  against  it.  Tiie  presence  of  sugar  in  the 
lluid  depends  not  only  upon  a  condition  of  hyperglycemia  but 
aNt)  u\hn\  interference  vvidi  the  selective  action  of  the  choroid 
l)Ie.\us. 

More  imiiortant  is  the  appearance  of  acetone  in  the  fluid. 
This  is  never  present  except  in  ca>es  of  cmna  or  unless  coma 
is  impending.  In  ob>cure  case>  of  coma  in  which  a  sample  of 
the  urine  cannot  be  obtained  very  great  assistance'  may  there- 
fore be  afforded  by  the  exatiiination  of  the  cerebrospinal  fluid. 
Diacetic  aci<l  is  found  more  rarely,  and  its  presence  is  always 
an  indication  of  the  extreme  j/ravitv  of  the  case. 


ur.s:mia 

In  ur.-cmic  convulsions  and  in  eclampsia  the  cerebrospinal 
pressure  is  raised  and  the  amount  of  fluid  increased.  Kveii 
in  unemia  vviihoiit  (.onvnl-'ions  the  pressure  is  often  above 
normal.     In  a  mmiber  of  cases  of  urannic  convulsions  a  con- 

146 


GENERAL  DISEASES 


147 


siderable  lymphocytosis  has  been   found,  but  this  is  not  a 
constant  feature. 

In  all  uraiuic  states,  wlicther  accompanied  by  convulsions  or 
not.  an  estimation  of  the  urea  content  of  the  cerebrospinal 
fluid  is  of  the  greatest  value  both  in  diagnosis  and  prognosis. 
It  parallels  in  a  remarkalile  way  the  urea  content  of  the  blood, 
but  while  the  estimation  of  the  latter  is  a  matter  of  .some 
dirticuity  demanding  refined  methoils  of  chemical  analysis, 
that  of  the  former  can  lie  carried  out  with  the  greatest  ease. 
An  examination  of  the  cerebru.spinal  fluid  thus  affords  a 
reatly  method  of  estimating  the  degree  of  urea  retention  in 
the  lx>dy. 

The  normal  urea  content  of  the  cerebrospinal  fluid  varies 
from  o.oi  to  0.05  or  o.of)  per  cent.  Anything  alxjve  this 
must  I)e  regarded  as  indicating  some  degree  of  urea  reten- 
tion. According  to  Mestrezat  cases  of  renal  impermeability 
to  urea  without  any  symptoms  of  ura?mia  may  show  a  urea 
content  up  to  o.i  per  cent.  In  tnie  urremia  the  urea  content 
may  be  anything  from  o.i  to  of,  per  cent.  The  variations  in 
the  amount  of  urea  closely  correspond  with  those  of  the  bhuid. 
In  practice  it  is  often  found  that  ca.scs  of  cardio-va.scular  dis- 
ease .show  signs  and  symi)toms  highly  suggestive  of  true 
ura^mia.  but  in  such  cases,  as  Canti  has  pointed  out.  the  urea 
content  of  the  spinal  fluid  remains  normal.  An  estimation 
of  the  cerebrospinal  urea  is  therefore  a  valuable  aid  in  diag- 
nosis, and  in  cases  which  are  seen  for  the  first  time  in  a  state 
of  coma  it  may  be  the  only  method  available. 

Xor  IS  it  of  any  less  value  in  questions  of  prognosis.  .Ml 
the  work  which  has  l)ccn  done  so  far  tends  to  prove  that  the 
higher  the  urea  content  the  graver  is  the  prognosis.  The 
critical  (Ignrc  may  I)e  taken  as  0.3  per  cent.  .According  to 
Mestrezat  cases  which  exceed  that  Hgure  are  almost  invariably 
fatal,  whereas  those  1h.>Iow  that  figure  mav  Iw  regarded  as 
curable,  and  many  of  them  recover.  Soper  and  Grant  ar- 
rived at  somewhat  similar  conclusions.  They  consider  that 
if  the  urea  content  only  reaches  o. r  per  cent,  no  prognostic 
conclusions  can  l)e  drawn.     Retween  0.1   and  0.2  per  cent. 


MICROCOPY    RESOIUTION    TEST   CHART 

ANSI  onrt  15)0  TEST  CHART  No    2 


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■  ,1 


*  •! 


many  of  the  cases  proved  fatal.  Alujve  0.2  per  cert  all  the 
cases  slioueil  severe  urainia  and  ran  a  >peeily  couri 

The  e>liniali(in  of  tlie  nrea  is  cnnveniently  carried  ont  liy 
tile  lupohroniite  niethnd.  To  5  c.c.  of  cerebrospinal  linid  are 
added  _'3  c.c.  of  40  per  cent.  piiia>siuni  liydrate  and  _'._'  c.c. 
of  hroniine,  and  tlie  re^nlt  is  read  in  a  Dorenuis  nreoineter. 

Wells,  nsins;  the  more  delicate  urease  method  as  modified  hy 
\'.ui  Slyke,  found  that  there  was  a  close  relation  hetween  the 
urea  nitrogen  and  the  total  non-protein  nitrogen  hotli  in  the 
Mood  and  the  spinal  lluid. 

The  retention  of  chlurides  in  the  hody  so  characteristic  of 
ura-niia  is  rellected  in  the  cerehrospinal  lluid.  The  normal 
chloride  content  of  the  iluid  is  0.7^^  jier  cent.  In  uraemia  and 
eclampsia  this  may  he  increased  t(j  o.S  or  more. 

.\fter  eclamptic  seizures  considerable  (|uantities  of  lactic 
acid  may  Ir-  present  in  the  lluid.  as  nuich  as  4  per  cent,  having 
been  recorded.  In  the  normal  fluid  there  is  either  none  present 
or  onlv  the  merest  trace.  The  riYehuann  lest  is  not  suitable 
for  demonstrating  the  ]ire-euce  of  lactic  acid  in  the  spinal 
lluid,  and  that  of  Keichmann  .-hould  be  u-^ed.  M  least  10 
c.c.  of  spinal  lluid  are  treated  with  5  c.c.  of  t)6  per  cent,  al- 
cohol, and  filtered  after  an  inter\al  of  u  hours.  The  filtrate 
is  washed,  treated  with  hot  alcnhol,  and  dried.  The  residue 
is  iilaced  in  a  te-t  tube  to  which  are  added  3  drops  of  deci- 
normal  ILS(),  and  then  10  c.c.  of  etiier.  the  whole  being  well 
shaken.  A  dilute  solution  of  ferric  chloride  is  jilaced  in  two 
test  tubes,  to  one  of  which  is  added  the  etherial  extract.  .\  ])ale 
golden  color,  which  can  be  CMm])ared  with  the  control  tube, 
indicates  the  presence  of  lactic  acid. 

CHOREA 

The  etiologv  of  chorea  is  >till  uncertain.  Tt  certainly  ap- 
pears to  bear  a  close  relation-h.i|)  to  acute  articular  rhcuinati.sm. 
.Several  attempts  ha\e  been  made  to  associate  chorea  with 
svphilis.  In  order  to  try  to  settle  these  points  several  .small 
scries  of  ob-ervatioii<  have  been  ui;ide  on  the  spinal  fluid. 

Such    obser\ations    conclusively    prove    that    .syphilis    bears 


GENERAL   DISEASES 


149 


no  ct..,Io,i,r,cal  relation.,!,;,,  to  the  disease.  Koplik  exa.nine.l 
the  spinal  iluuls  in  ,0  cases,  and  in  all  the  Was.ernuinn  re- 
action was  nes:ative.  Marie  an.l  Chatelin  in  191J  and  Conihy 
III   i<>i5  had  already  oinained  similar  re-nlts. 

In  many  cases  of  chorea,  however,  there  is  some  evidence 
of  the  action  of  an  irritant  on  the  central  nervous  system  as 
shown  hy  tlie  presence  of  a  lencocytosis.  A  number  o'f  !■  rench 
observers -Thomas  an.l  Tinel.  Claude,  and  others  -  have 
described  tlie  occurrence  of  a  marked  Ivmphocvtosis  X,,  ex- 
tensive scries  of  cases  has  In^en  reported',  however.  In  a  small 
series  of  ;  cases  [  found  the  Ihii,!  perfectlv  normal,  except 
that  HI  one  case  there  was  a  sli.t,dit  Ivmphoi'vtosis  of  1;  per 
c.  mm.  In  a  series  of  ,0  cases  .Mor>e  and  l-lovd  had  three 
with  counts  of  iN,  _«^,  ,-,n(I  j^ 

Many  observations  have  been  made  on  the  bacteriolo-v  of 
Uie  nuid  durin-  life,  but  with  ne-ative  results.  Povnton'and 
Paine  ..,ccec<led  in  isolatin-  the  or-anism  which  thev  term 
the  diplococcus  rhcumaticus  from  the  spinal  Oui.!  post-m.,rtem 
m  three  cases  which  died  of  acute  rheumatism  complicated  by 
chorea.  I  hey  fiiiurc  these  or-anisms  to-ether  with  the  cel- 
lular exudate  in  their  paper. 

MUMPS 

It  mrVht  be  th,,u-ht  that  mum,,s  was  hardlv  the  tvpe  of 
'h.>ease  m  which  chani^es  in  the  cerebrosp-,al  (luid  nii-dit  be 
expected.  .\nd  Net  in  a  considerable  number  of  cases^ien- 
m.jreal  complications  may  occur.  These  \arv  in  intensitv  fn^m 
restlessness  with  siccus  of  cerebral  irritation  to  .lelirium  and 
pnralysis  of  cranial  nerves.  It  is  bnt  natural  that  the  cases 
with  cerebral  complications  are  tlie  onK  ones  in  which  a 
systematic  examina;ion  of  the  cerebrospinal  flui.I  has  hocn 
conducte.1.  but  in  tbe^e  ca<es  a  verv  constant  change  ha,  been 
observed,  nameh-  a  o-reat  incnvne  in  the  nnnilH.r  of  Ivninho- 
cytes  without  a  corresponding  increase  in  the  Hobulin  '  There 
mav  be  several  th,„v<„„l  ,ells  ,.„•  ,-.  mm.,  over  00  per  cent 
of  which  are  Ivrnpho,.,,..,  TIum-  chan^..  i,ase  been  de- 
scribed by  a  number  of  French  writers  such  as  Dopter  and 


=N; 


.Is 


P 


,50        PHYSIOLOGY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

Sicard  as  occurring  in  cases  of  involvement  of  the  cranial 
n^ves  with  an  accompanying  herpes.  FeiHng  has  p.mted  ou 
that  a  Ivmphocytosis  may  occur  in  mumps  where  there  has 
been  no 'evidence  of  an  organic  lesion  of  the  nervous  system. 
S^,e  experiments  by  M.  H.  Gordon  serve  to  illustrate  the 
distinct  affinitv  which  the  virus  of  mumps  has  for  the  men- 
inges ratients  suffering  from  parotitis  were  made  to  gargle 
their  momhs  with  saline  solution.  The  saline  was  passed 
through  a  Berkefeld  filter  and  was  found  to  he  ster.le.  It 
was  then  injected  into  the  brains  of  monkeys,  "/^l^  the 
monkevs  injected  developed  meningitis,  and  m  one  the  flmd 
during  life  contained   ..300  cells  per  cm-.,  of  which  82  per 

cent,  were  Ivmphocytes. 

In   10.^  r.ordon  described   four   fatal  cases  of   dlness  oc- 
curring in  children,  in  which  the  chief  feature  was  symptoms 
of  marked  cerebral  irritation.     All  of  the  cases  showed  acute 
interstitial  parotitis,  but  they  were  in  no  way  typical  exaniples 
of  mumps,  for  the  glan.lular  tissue  proper  appeared  to  have 
entirelv  escaped.     The  cerebrospinal  fluid  was  examined  and 
showed  a  very  marke.l  lymphocytosis,  in  one  case  there  being 
6800  cells  per   c.  mm.     The  pia   mater   showed   slight   con- 
gestion, and  a  variable  degree  of  lymphocytic  infiltration,  but 
no  definite  evi.lence  of   meningitis.     There  were  no  lesions 
sngcre^tive  of  poliomvelitis  in  the  brain  or  cord.     The   foci 
in  the  parotids  consisted  of  dense  infiltration  of  lymphocytes 
so  marked  that  in  places  the  glands  closely  resemblcl  a  lymph 
node      Tn  spite  of  this,  however,  there  were  no  clinical  signs 
of  parotitis  during  life.     Gordon  is  of  the  opinion  that  either 
the  condition  was  the  result  of  an  unusual  action  of  the  virus 
of  mumps,  or  that  it  was  a  f.^rm  ..f  a  disease  which  has  not 
hitherto  been  reco.gnized.     The  marked  cerebrospinal  lympho- 
cytosis occurring  apart  from  mumps  was  a  very  striking  fea- 
ture   and  the  possibility  of  other  cases  of  this  disease  being 
encountered  should  l>e  borne  in  mind.     Tn  such  cases,  of  course, 
tuberculous  meningitis  must  be  first  excluded. 


GENERAL   DISEASES 


151 


PNEUMONIA 

Few  observations  luive  been  made  on  the  spinal  fluid  in 
pneumonia  apart  from  tliose  cases  which  show  evidence  of 
developing  pneumococcal  meningitis.  Rohdenburg  and  Van- 
der  Veer  made  a  series  of  observations  on  the  condition  of  the 
fluid  in  all  cases  of  pneumonia  admitted  to  hospital,  whether 
these  manifested  sjmptoms  of  meningeal  irritation  or  not. 
The  only  case  of  the  series  which  showe'l  meningeal  symptoms 
was  the  only  one  with  a  turbid  spinal  fluid.  The  remaining 
cases,  however,  showed  \arious  pathological  changes  in  a  re- 
markable number  of  instances.  The  observers  considered  that 
these  changes  were  of  distinct  prognostic  value.  Should  fur- 
ther work  confirm  these  results  it  may  furnish  the  clinician 
with  an  additional  means  of  arriving  at  a  correct  prognosis 
in  a  disease  in  which  prognosis  is  always  diflFicult. 

Pneumococci  were  found  on  culturing  the  fluid  in  a  much 
higher  proportion  of  the  fatal  cases  than  in  those  which  re- 
covered. Of  the  fatal  cases  S7  per  cent,  showed  pneumococci 
in  the  fluid,  whereas  those  which  recovered  only  gave  13 
per  cent.  The  average  cell  count  of  those  who  died  was  212; 
that  of  those  recovering  was  50.  In  the  sterile  fluid  the  count 
was  much  lower.  There  is  need  for  further  observations  of 
this  nature  on  other  series  of  cases. 


SLEEPING  SICKNESS 

Of  all  the  observations  on  the  cerebrospinal  fluid  none  have 
been  of  greater  importance  than  those  in  sleeping  sickness. 
For  it  is  now  known  that  sleeping  sickness  is  but  one  mani- 
festation of  that  very  widely  spread  tropical  disease,  trypan- 
osomiasis, and  that  the  fatal  symptoms  do  not  make  their  ap- 
pearance until  the  trypanosomes  have  succeeded  in  passing 
from  the  blood  to  the  cerebrospinal  fluid. 

Tn  many  ways  the  disease  Iiears  a  close  resemblance  to  gen- 
eral paresis.  Tn  Ixith  conditions  the  nervous  lesions  may  be 
preceded  for  a  l(Mig  time  by  a  systemic  infection.  In  both, 
one  of  the  chief  features  is  a  lymphocytic  infiltration  of  the 


IS2        I'MYSIOI.OGV   AND    I'ATIIOIOr.Y  OF   TIIF   CnRnnROSIMN'AI-   FLUID 


'^rt[ 


t" 


1  !*■    ' 


tncniiif,a>s  and  the  jjcrivascular  lyinpliatic  slicatlis.      In  both  a 
lyiiipIiiH-vto.-is  (n'Ctirs  in  the  eerehni-pinal  lluiel. 

'I'he  onhnary  worl-er  rarely  has  tlie  opixiriuiiily  of  (il).-erv- 
iiig  such  a  case,  hut  it  appears  that  tlie  cyt«)l«>t;ical  picture  in 
the  tluid  is  similar  to  that  ot"  general  parens.  The  most  char- 
acteristic feature,  ho\\e\er,  is  the  presence  in  the  s]iinal  lluiJ 
of  'rr\i)anos()nia  i^anihieu'-e. 

TRICHINOSIS 

The  ahsolute  diapio-is  of  trichinosis  is  not  usually  a  simjilc 
matter.  Tl;e  -cncral  ~}niptoms  and  cr^pecially  the  character- 
istic cosinophilia  in  tlie  Mood  may  jioint  stnm.i^ly  to  the  proh- 
ahility  of  .an  infection  with  Trichina  spiralis,  hut  unless  a 
piece'of  muscle  he  e\ci-ed  and  the  larva-  demoustrateil.  ahso- 
lute certainty  can  hardly  he  attained. 

It  has  lately  iiccn  di-covcred  that  in  a  numher  of  cases  an 
early    infection    of    the   cerchro-pinal    lluid    occurs.     Strange 
thouf^h  it  may  appear,  the  larv;e  have  the  i^ower  of  making 
their  way  into  the  spinal  lluid,  and  can  he  demonstrated  there 
with  ease.     Lintv  reports  three  ca-es  in  which  several  motile 
embryos  were  present   in  every  field  of  the  centrifuged  de- 
posit, althou.^h  there  w.is  no  increa-e  of  the  cells  or  glolmlin. 
If  further  work  .-hows  that  this  cerehrcspinal  inva.-ion  is  an 
early   and   constant    feature,   a   new   and   valuable   means   of 
diagnosis  will  have  been  placed  in  the  hands  of  the  clinician. 
Although  eosinophils  are  so  numerous  in  the  blood  in  this 
condition!  they  have  not  been  reported  as  occurring  in   the 
cerebrospinal   iluid.     Occasionally,   however,   the  .spinal   lluid 
may   respond   in   this  way  to  infection   by  animal   parasites. 
Two  cases  of  infection  of  the  brain  by  Cysticercus  cellulos.x 
were  accompanied  by  a  marked  cosinophilia  in  the  cerebro- 
spinal fluid  as  well  as  in  the  bloo<l.     Such  a  condition  may  be 
t.akcn  as  pathognouKinic  of  animal  parasitic  infection  of  the 
central  nervous  system. 


Cl-NKRAI.    IJISl-ASKS 


153 


REFERENCES 

C'ami.  K.  (i. :  'Die  tiic.i  content  of  tlii-  ccrilitosiiinal  lliiiil,  willi 
siiccial  rclciciicf  to  ilu'  iliai^nor-is  of  iiriuiiia.  Kancct.  1916,  I,  p. 
366. 

Claude,  II.:  Ikiix  cas  dc  I".hori.'e  ]icr-i-^tanto  avcc  sialics  de  Ic-ions 
anatoniii|nes  k',i;ircs  (k'  -ysiiinc  niMvcux.     Rev.  nciirol.,   lyoc).  X\  II. 

p.  O.V- 

Doptcr.  Taraly^ie  facialo  ourlicnnc;  Iynipliocyto>e  dn  lupiide 
ceplialo-rachiditn.  lUill.  ct  nioni.  Soc.  nicd.  d.  hop.  dc  Paris.  1904, 
XXI,  p.  912. 

Fcilins.  .\.:  Tlie  li!ood  and  tlic  ccvcbrosiiinal  fluid  in  ninnips. 
l.ancct,  T()i3.  II.  p.  71. 

Fcilini;,   A.     Munijis:   a  critical   review.     Quart.  Jour.  Med.,   1915. 

VIII,  255. 

Ciordon.  M.  IT.:  A  f.itat  illness  in  cbililrcn  associated  with  acute 
interstitial  parotitis.     Lancet.   i')i.V  H.  p.  275. 

Cordon,  M.  li.:  Reports  I.oc;d  (iovernment  r.onrd.  Xe^\•  Scries, 
Xo.  (/i.   1014. 

Tlojikins.  .\.  IT.:  Ti'c  su-ar  content  of  the  spinal  fluirl  in  menin- 
gitis and  other  diseases      .\ni.  Tour.  Med.  Sc.  10'.'.  CI.,  p.  ^27. 

Koplik,  X.:  The  ctioloe-ical  relationship  <if  syphilis  to  the  chorea 
of  .«;ydcnhani.     Arch.  Tediat..  101;.  XXXIf.  p.  .^7^. 

T.intv,  \V. :  Trichinosis  and  the  ccrehrospinal  iTuid.  Jour.  Am. 
Med.  .Assoc.  If)i6.  I.XVT.  p.  185^. 

Marie,  P.  and  Chatelin.  C. :  Sur  les  eft'cts  favourahles  dcs  in- 
jections intra-veineuses  de  ■^alvai'san  dans  2;  cas  de  Choree  de 
Sydenham.     Pidl.  de  rAca<l.  de  ined..  Paris.  tot2.  T.XVTTT,  p.  507. 

Mor=e,  T.  T..  and  Floyd.  C. :  A  study  of  the  ctiolo!::y  of  chorea: 
Am.  Jonr.  Dis.  Child.,  ioi<'>.  XTI.  p   fit. 

P(n-nton,  F.  I.  and  Paine.  .\ :  Some  ohservations  on  the  nervous 
iirinifeslatinns  of  acute  rhenni;iliMU.     T.ancet.   100;.   II.  p.   ijCio. 

Reichmann;  Znr  Physiolo-ric  und  T\-!to1(-c:ie  des  T.iquor  cerehro- 
spinalis.     Dentschc  7eitschr,  f.  Xervenheilkunde  TM.  42.  TT.  1  w.  2. 

T^ohdenhurcrh.  E.  T..  and  Vander  Veer,  .\.:  The  spinal  fluid  in 
p!ieunionia.     Jour.  Am.  Med.  .\s=oc.     lOL'.  T.XI\'.  1227. 

Sicard.  T.  ;\.:  T'U  ces  dorcillous.  avcc  zona  du  trijumcau  et 
lymphocyto'-e  rachiiliemi' .  P.idl.  et  mem.  Soc.  .Med.  cPbAp  de  Paris, 
ion;.  XX IT.  p.   13^. 

\'an  SlvKe  ;md  Cid'en:  .\  nernnne:-t  prenarafion  of  urease  and 
its  use  in  the  detevminafion  of  urea.  Jour.  P.iol.  Chem.  191''.  XTX. 
p.  221. 

Soper.  W.  B.  and  Grant,  S. :     The  urea  content  of  tlie  spinal  flujd 


IS4        niVSIOI.OGY   AND   I'ATlini.OCV   OF  Till-    CliRKKROSl'lN AI,  FI.UII) 

with  s|)ccial  reference  to  its  di.ik'iiosl'c  and  pro-nostic  significance. 
Arcii.  Int.  Med..  i<)\2.  XIII,  p.  i.V- 

Thomas  and  Tind:  llcniichorOi'  ct  si-iu-s  do  K'sion  orpiniiiue  dit 
sy>lenK'  iierveiix  central.  I.ynipliDCX td-e  dn  liiiuide  cephalo-rach- 
idicn.     Rev.  Xenrul..   i<><^).  X\II.  p.  63S. 

Waterhouse.  R. :  Cysticercus  celhdosie  in  the  central  nervons  sys- 
tem.    Ouart.  Jour.  Med..   1913,  VI,  4^k). 

Wells.  A.  C :  Studies  of  nitro.L^en  partition  in  the  hlood  and 
spinal  flnid.     Arch.  Int.  Med.,   191.=;.  ^^'I-  P-  ?77- 

Zweifal:  Zur  Anklaruni,'  der  I'.klampsie :  Archiv.  f.  Gyn.,  1905, 
76.     (Quoted  by  Kaplan.) 


ClIAl'TKK  XX 


TIIKRAI'ELTICS 


Lumhar  puncture  was  origuially  introduced  by  (Juinclse  with 
the  object  of  relieving  intracranial  pressure.  In  the  ^3  years 
which  have  elapsed  since  then  interest  has  jjcen  mainly  cen- 
tered on  the  diagnostic  possibilities  of  the  examination  of  the 
cerebrospinal  Huid.  Recently,  however,  therapeutics  have 
again  claimed  atteni.on,  and  a  number  of  important  advances 
in  this  direction  have  been  made. 

lUMBAR  PUNCTURE 

The  original  conception  of  lowering  intracranial  pressure 
by  lumbar  puncture  has  been  widened  and  applied  to  a  variety 
of  conditions.  At  the  same  time  it  is  recognized  that  the  op- 
eration is  not  devoid  of  danger,  and  that  certain  precautions 
must  ])e  observed.  The  possibility  of  accidents  occurring  dur- 
ing the  withdrawal  of  fluid  in  cases  of  cerebral  tumor  has  al- 
ready been  discussed. 

In  a  large  number  of  diseases  symptoms  of  increased  intra- 
cranial tension  may  appear,  and  in  many  cases  relief  of  these 
symptoms  may  be  afforded  by  lumbar  puncture.  It  is  only 
possible  to  give  the  briefest  summary  of  such  cases. 

The  value  of  lumbar  puncture  in  ura?mic  coma  and  eclamp- 
sia has  already  lieen  commented  on.  Many  cases  have  been  re- 
ported in  which  brilliant  results  have  followed  this  simple 
operation.  Thus  Wilson  described  two  cases  of  puerperal 
eclampsia  which  had  each  had  more  than  20  convulsions. 
The  patients  were  in  a  very  serious  condition  and  were  rap- 
idly passing  into  a  state  of  coma.  All  methods  of  treatment 
had  been  tried,  but  without  avail.  The  withdraw.nl  of  40  ex. 
by  lumbar  puncture  was  followed  by  speedy  relief,  the  con- 

155 


IS')      i'insi()i.()c,\  .\\i)  ^.\^ll()l,l)(.^  ov  tin.  ci  rii'.rdsi'in.m,  ri.i  id 


i    V. 


■h 


t 


if 


ii 


=  ».i 


vuKiuiis  co;i-i.'(l.  tiK'  iliiwitciuil  imiu.i  |i.i--i'(I  mT,  ;m>l  li. itli  pii- 
lii'iit>  iii.nk'  .1  i;m,i.1  riHMM'r\.  I  Iki'.c  •i.Tn  :\  •iniilar  rr~nlt  in 
;i  (.'a-i'  '<\  i-i'iniiu'iiri;  ;;-  m-.-mic  CMina,  ::nil  ilu'  umIim;!  i^  wrll 
wiriliy  (if  trial  in  vvvv  ra  r  in  uln'fli  iIktc  i-  n-a-iMi  tu  lic- 
lii'W  that  a  innililinn  m'  nrrhr.il  diK-m.i  iinv  cxi.-t. 

'I'lic  iK-r^i-tiiil  Iu:h!;n.-::i'~  \\ii''li  -^Mimiimr-  c  in-titnti'  .-o 
lr"nI)'i'-nnK-  an  arr'inipaiiinirnl  ci'  anainia  ma,  1\'  ^vcally 
rt-lifM'il  \>\  I'lml'at  i>nnct;nv.  !M-"ni  ;  to  f  i' r.  m'  tlnid  inav 
In-  w  ithilrawii  at  ii'''T\  al<,  n-'irvin"  llu'  triiM''n  witiiin  tlu- 
>\<u\\  :u]>\  all"\\)no-  ^h^^  jii'ra,  f.niial  C' iii(Ii:iii>;->  t.i  ri'tnrn  ti>  a 
^tatr  ct"  ndrma]  I'-pi'lilirii'm.  'Mk'  lu.^lac'H'-  <<'■  nt'nra-i'K'in'a 
ami  ciIkt  ncrvi'ii'^  cuii'liii.ii ,  inav  Ik'  lii-iielitiil  !i'.'  similar 
Iroatmrnt. 

A  ti't  uin'i'mmMii  nnnit'i-  taiinn  nf  ili  tn'.'lu-il  i'ltratTa.nia! 
li'iNiim  i>  (!i~tnr!iani\'  ni'  tlio  an('ito!v  miTliaiii-'m.  iV-afiuss, 
tiiuiitu-,  anil  an'!:l.r-.  m  vi:.,.-.!  u\:'\  !:;■  a-;Mri:'t!'(1  with  lii^h 
ctTcbm-pinal  pre--tiiv,  a'i:l  ilv,'  -ymp1"m-  mny  lie  w-nilcrfnily 
rrlit'sr.l  1>\  a  '-eric-  ..i"  'rni'r,!-  ]yv<.-\'\u'-.  P. ''.in-!  i  ikv-crilns 
ii"o  ca-o.  a"C(|  ■--.  \\]]''  li.-'.i!  I'.tn  a  t\v-\\  nvtv  fi  t  nvtT  two 
yi-ar<.  Imt  v.Iim  cmmM  luar  a  \(iirc  at  _m  r.tn.  ;it'irr  tlitvc  liimliar 
pnm-inrc-;.  In  tlri^  ra.c  15  •■•.(•.  ''f  lln'^l  wrn'  \\itl'<lra\vn  on 
t-acli  (iccasiiii.  'i'lic  mn-^t  prnmi^ini,'  ca-(.'>  arc  tl'.cse  of  per- 
sistent tinn'tn-.  An  intimito  rflalioii^^liii)  cxi  t-;  lictweoii  the 
pressure  m-'  tlie  ctTi'TM-ninal  Hnii!  ati.l  tJiat  oi'  the  i)(.-ril\-mpli 
and  cm'Mlvmph  n\'  i!ii'  !a'.\  r-nibiiu'  canal,  and  -  .mc  cases  of 
tinnitn^  and  vef.i^n  ;ire  un  I 'nli'.c'lx-  dne  Id  di<inrlianre  nf 
tlii>  relatiiinvliip.  'I"\plin^  t'ever  may  -Dmetinics  l>e  aceom- 
panicfl  !i\-  dea, fnr---.  which  i--  n.-na'lv  ••■rcallc  relieved  1)\-  Inm- 
har  pnnctnre. 

ConviiKiiiii^  in  children,  "i  which  the  eti.ih".'-^-  is  frefuiently 
so  ind''Ierni'n,'r.e.  !na,\-  ct'len  hi'  ninre  cnicM}-  rclie\'e  1  hy  Inni- 
liar  pn-u'tnre  than  Ic  an\-  ntlier  thrrapnnh-  iniTiscre.  In  one 
civt-  i.f  ,-,  .IV  I'Kii.'i^  ;■!  rni  int'.-in;  ihc  nrrient  wa<  ;dnii><t  ninri- 
hnnd  a  the  r>-;;]l  (  '  a  !-n  •;  crir  ..f  !iu.  d'l'c  f..n'an.dlc 
^hnwed  nnrked  hitl;;!nu-  anil  the  intracranial  prc-;-^.nre  wa--  e\  i- 
dcntlv  Cl'n■-idera^1^•  incrca-^ed  Xvithdrawal  "f  a  dear  and 
apparcntlv   norma!   lliiid   under  pressure  prevented   the  child 


TIlrRAI'tlTICS 


IS7 


fnun  Ii;uiiijj  any  mure  \]\-.  fur  a  uock.  At  tlu'  tud  (if  lliat 
liiiK'  i1k'\  nltinii'd,  and  tlu'  fculaiu'lli.'  u:i>  a,^.iiii  fuiuid  In  lie 
l)ul,t;iii,L;'.  A  -iTnnd  u  illidiau.il  ua^  a^ain  ^ii  ■i.c-^inl  fur  aii- 
(itlicr  utrk.  Oucl-  iiiori-  tin-  li:^  ri'tunud,  Iml  the  third  iniiic- 
ture  effected  a  cc<ni]il''te  cure,  and  tlie  child  lia^  r  i.iained  well 
ever  siiifc.  Ajipareiitlv  a  di  turiiam-e  in  the  i'.itracraiiial 
(•(|iiilil»rii;(ii  Iiad  ucrnrred  \\In\li  \va>  inn\l\  tenii»irary,  and 
when  the  immediate  danL;er  had  lieeii  tided  mer  the  di>tnrlied 
lirdanre  n;iinnd>  id  ii.  nrd.  It  i  iiruliaMe  that  tlie>e  disturh- 
ance-^  mav  n;idil.  I'coiir  in  cliihhui.  and  in  lumhar  ])nnctnrc 
v,e  ha\e  a  rea'l\-  v.;h;ilile  i.haii'  uf  dealing'  with  the  einert;ciicy. 
'I'hev  are  exaiiiiile  of  a  mild  fcrm  "i  what  has  ah'eady  heeii 
(k'-crilied  a-  1i\;icr-.e("i"eti\  e  hyiii'iH'e|iha!u--. 

In  rare  ca-.--  it  ma\'  hai>iieii  that  a'lhdii.i^h  there  ;ire  marked 
si^n-;  of  lii.Cih  intracranial  tension  Inmliar  i)iinctnre  alTord>  nu 
relief  ;md  tho  |ire-.-inv  i>\  tlie  >;)inal  lluid  due-'  nut  a])]iear  to 
lie  rai>ed.  in  >U':h  ca-e-.  whi.h  are  really  eNamjiles  <if  in- 
ternal cr  dh  inuiiw.'  hydr(ice|ili;dns.  it  may  he  jiernii~-^ilile  to 
pnnetnre  the  latend  ventricle  thrdn,;;]i  the  anleridr  fd-jtanelle. 
I'ischer  has  de-cri'ied  a  case  uf  very  >evere  cunvnNinns  tol- 
lowinij  whudpini;  cuu^h  in  a  hahy  uf  N  nidnths.  All  torms  ul 
treatment  inrlndinj^f  Inmhar  ]);inrture  were  uf  no  avail,  liut 
the  withdrawal  uf  _>j  c.c.  of  clear  cerehmsjiinal  lluid  from  the 
ri.sjht  ventricle  uf  the  hniin  was  fdlluwed  liy  an  immediate  ces- 
sation of  the  Cdnvnlsinns  and  tlie  complete  recovery  of  the 
patient.  The  needle  was  intnulu-ed  ddwn wards  and  towards 
the  middle  line  to  a  depth  of  i.S  inches  ;it  an  ant;le  of  _'0 
de.^recs. 

The  question  of  the  advisahilitv  of  lowcrinc^  intracranial 
pressure  liv  lumhar  ])ui!cture  in  cases  of  cerebral  tumor  is  a 
dchatalile  one.  Tt  has  already  heen  eiuphasi/ed  that  this  is 
the  one  condition  in  which  the  t^reatest  caution  nni-t  he  ex- 
ercised. Tumors  in  the  posterior  fos-a  should  not  he  de- 
compressed in  this  way.  The  danjjcr  is  too  preat,  and  in  any 
case  onlv  a  verv  small  (|uantity  of  lluid  could  he  withdrawn. 
In  tumc^rs  situated  in  the  anterior  and  middle  cram'al  t'ossa-. 
however,  a  sjiinal  decompression  sometimes  ])rovides  a  useful 


}   '■ 


;, 


rVJ 


S' 


li 


•i 


|: 


158       I'll^SIOI.ooV   AND  I'ATIIOMK.V  OF  Tilt  CbRtBROSI'INAL  FLUID 

and  >imi»lc  imans  of  rclicv  iiij,'  the  luailache  and  tlic  optic 
miiriti>.  A  \:U'^c  iiii.iiitiiy  oi  lliiid  should  iml  l»c  uillidrawii 
at  (line,  lull  a  mimlH-r  oi'  .>inall  aiiioiiius  011  lre(|ui.'iit  occasions. 

I.uinljar  puncturo  lia>  j)ri)\t.(l  a  ii>ct'itl  measure  in  a  variety 
of  war  injuries.  Many  ca>es  of  hernia  cerebri  have  derived 
lundit  fn.ni  repeated  tappinj;s.  hut  jjreat  caution  nnisi  In;  used, 
a^  lliere  is  a  (h^tinct  danj,'er  tliat  locah/ed  jMickets  of  pus  may 
licionie  (h-'  eniinatecl  if  tlu'  prosure  is  >uddcnly  lowered.  In 
concu.ssion  and  shell  shock  the  cerebrospinal  pressure  may  Ik; 
markedly  increased,  and  in  such  cases  lumbar  puncture  will  be 
f(jund  of  great  value. 

A  curidU-.  and  inlerestinj;  e\anii)le  of  the  (Ii\erse  uses  to 
which  luiiiliar  ])uncture  may  be  |)Ut  is  afforded  by  a  case  re- 
cently puljlished  by  Costa.  The  case  was  one  of  podalic  ex- 
tr.iction  with  central  placenta  jir.'cvia.  The  head  of  the  child 
Could  nut  be  delivered,  so  lumbar  i)uncture  was  performed. 
As  the  head  p.issed  tliroti^ji  the  inlet  t1uid  ijtished  from  the 
needle  and  cr;i>ed  when  the  heail  emerged.  It  is  estimated 
that  the  diameter  of  the  head  can  be  diminished  0.5  cm.  by 
til  is  means. 

THE  SERUM  TREATMENT  OF  MENINGITIS 

The  mortality  from  menin,i,'ococral  meiiincjilis  used  to  av- 
eranfc  about  So  per  cont.  IJoth  in  the  .American  and  in  the 
r'nt^lisji  epidemics  it  was  seldom  th.it  the  death  rate  fell  below 
75  per  cent.  In  1907,  however,  Simon  Flexner  introduced 
tlie  intraspinal  use  of  antimeninf]^ococcal  serum,  and  the  mor- 
talitv  at  once  showed  a  marked  and  sudden  drop.  Tn  most 
recent  epidemics  the  fic^ure  has  ranj,'ed  between  25  and  30  per 
cent. 

In  the  winter  of  T014-T5  at  the  outbreak  of  the  war  there 
were  a  larcfc  number  of  cases  of  epidemic  meninj^itis  owinp;  to 
the  fjreat  Ixxlies  of  men  collected  in  barracks  and  camps. 
These  cases  were  treated  bv  the  injection  of  serum,  but  the 
results  were  very  unsatisfactory.  The  same  was  true  for  the 
cases  which  came  under  mv  observation  in  Belgium.  Tn  these 
latter  cases  we  got  quite  as  good  results  by  frequent  limibar 


( 


THERAPEUTICS 


«59 


puncture  as  hy  the  use  of  serum.  It  was  C(>n>iil«Te(l  at  the 
time  that  the  disappointing  resuUs  ucrc  pmliahly  <luc  to  the 
strains  of  meningococci  which  caused  the  tliscase  l)fing  (hf- 
ferent  from  those  with  which  the  serum  was  prci)arc(l.  >'ow, 
however,  it  appears  certain  that  the  serum  used  was  of 
poor  quality.  Fresh  samples  of  serum  were  obtained,  and 
the  mortality  again  fell  to  below  30  per  cent. 

Much  depends  on  the  promptness  with  which  the  serum  is 
administered.  The  earlier  in  the  disease  it  is  given  the  better 
are  the  results.  It  is  well  to  go  to  a  suspected  case  armed 
with  serum,  a  microscope,  and  the  means  for  preparing  a 
fdm.  A  diagnosis  can  I)e  made  at  the  Iwdsidc,  and  if  the  men- 
ingococcus is  found  the  serum  can  l)e  given  on  the  spot.  Even 
if  lalxiratory  facilities  are  not  available  the  scrum  should  Ik 
taken,  and  injected  if  the  fluid  is  at  all  turbid,  or  if  it  fails  to 
reduce  Fehling's  solution. 

The  tcchnic  is  very  simple.  .\  large-sized  lumbar  punc- 
ture needle  is  introduced  into  the  subarachnoid  space,  and  as 
much  or  more  fluid  withdrawn  as  it  is  intended  to  inject. 
This  is  absolutely  essential,  and  in  itself  is  a  measure  of 
proved  therapeutic  value.  A  sterile  glass  funnel  or  cylinder  — 
the  barrel  of  a  20  c.c.  syringe  will  do  perfectly  —  and  a  rub- 
ber tuln?  about  if>  inches  in  length  are  attached  to  the  needle 
by  a  metal  connection,  and  the  serum,  heated  to  body  temper- 
ature, is  run  in  by  gravity.  The  inflow  .nay  be  fast  or  slov.-, 
but  however  slow  the  temptation  to  use  pressure  with  a  syringe 
should  be  resisted.  If  not.  the  conser|ueni-es  may  be  di'^as- 
trous.  If  the  proper  amount  of  spinal  fluid  has  been  with- 
drawn, sufficient  patience  exercised,  and  the  patient  directed 
to  take  deep  breaths,  n,'  pressure  need  ever  be  used.  A  gen- 
eral anrcsthetic  may  be  necessary,  especially  in  children.  F-ach 
case  must  be  decided  on  its  own  merits. 

The  usual  dose  of  scrum  is  ,^0  c.c.  In  children  half  that 
qtiantitv  mav  be  used.  If  a  larg''  amount  of  fluid  ran  be 
withdrawn  the  dose  mav  be  increased  in  very  serious  cases. 
The  question  of  how  often  the  serum  should  be  given  is  an 
important  one.     It  should  certainly  be  continued  until  definite 


u 


5, 


k- 


ii  = 


ifiO        I'llVSlOUH.V   AND   I'ATlIO'.OdY   G  lU   CliREHROSlMNAL    FLUID 

clinical  iiiipnivcnK'iit  lias  taken  i)lacc.  ll  nni>t  lie  rcnicni- 
hcrcd  that  an  apparent  iinpiMvcinciit  may  occur  ahonl  llic 
sccdiid  or  thii'd  day,  fullnwcd  hy  a  relapse,  ll  is  ihcrefnre 
advisalile  to  ,L;i\e  the  serum  lor  at  lea^t  three  days.  In  severe 
cases  a  much  lar.^er  luinihcr  of  doses  will  he  reipiired.  I  he 
hactcrioloj^ical  content  of  the  lluid  is  not  \ery  reliable  as  a 
j,niide  in  pro_u;nosis,  and  it  must  he  horne  in  mind  that  the 
ventricular  lluid  mav  he  swarminj.,'  with  nuiiin;;ococci,  al- 
thou,qh  none  can  he  found  iu  the  >pinal  lluid.  Acute  men- 
inijitis  is  no  longer  re.s^arded  as  merel\-  an  infection  of  the 
menin,i;es:  it  is  rather  a  local  manifestation  o'  a  t;eneral  Mood 
infection.  It  is  L;oiid  |)r.'iclice.  tlierefore,  to  conihine  intra- 
venous with  intr.-i  iiin.al  injcciion-,  u-Iul;  for  that  purpose  ^d 
c.c.  or  more  of  the  -enun. 

The  hactcria  rajudlv  dcLViicrale  and  di-.in!c"Tate  so  that 
after  the  lir-t  injctiou  it  i-  not  u  iiall\-  jio-sii.ie  to  cljtain  a 
culture,  and  after  the  second  or  third  ihj  on^ani-ins  lose  their 
stainin,q[  reaction.  The  cytoloi^v  of  the  lluid,  however,  .-ilTords 
more  valnaMe  indii':itions  a-  to  the  -uci'e-;  c'  'he  treatment, 
and  it  is  most  intere-tinL-;  to  w.-.tch  dp  V.y  d.iy  the  cell  count 
,e[raduall\'  droppincf,  and  the  polymorphs  hein:.;'  re])!,'iced  liy 
l\inphi)C}-ies.  Tl:e  turliidit\  at  the  same  time  pr(';;re  -ively 
diminishes. 

Occ;isionall\-  the  ^eruni  mav  pr.i.hicc  ;ui  inllammatory  re- 
action which  i;  m,'i\  Ik  d''rr:>'u't  to  d:  !ip!;':i-h  from  a  tiaie  re- 
l;ili-e.  Tile  lluid  a,L,Min  hec-nu'-  f.ndiid,  ;ind  l,ir;;e  ni'inhers 
of  polvtnorphs  make  their  appcar.ance.  Tti  such  cases  the  es- 
timation of  the  ••u";ar  i-  of  I'Tcat  xriluc.  As  the  jiatient  im- 
pro\-es  the  Ft'hlin;.';-reducin';  power  of  the  Ih.iid  I'T.adtiallv 
returns.  In  ;\  true  relan-e  it  prompil\-  di-appears  owiuL,';  to  the 
renewed  activit\  of  the  ^itif.-ir-.-pliitinL;;  ori,^^ni<ms.  In  the 
p-etido-relapM'  due  to  the  irrit.'it'on  of  tli.'  -erum.  on  the  other 
hand,  the  l'"ehlini;--reducinL>-  i^wrr  !■   uu;irfecte<l. 

Tt  mav  happen  that  im  ^enim  is  a\ailahlc  for  treatment. 
Tn  -^nch  cases  himhar  T>nni-tnrc  -■hoidd  he  done  everv  dnv.  ;!t 
lea-t  .^T  c.c.  heiii;;-  w  ithdr.iw  ii.  'I  he  iihvsici;ni  is  often  too 
timid   in   the   amount   of   fluid   which,   he   withdraws.      1   have 


i 


h 


THnRAPnUTICS 


i6t 


drawn  off  70  c.c.  of  lluid  from  a  l)()y  of  i^  on  three  successive 
(lays,  and  tlie  only  effect  was  the  most  marked  rehef  of  the 
headache  and  other  clinical  syni])tonis.  It  is  somewhat  re- 
niarkahle  that  the  more  abnormal  the  Ihiid  the  les-^  disturb- 
ance does  its  withdrawal  produce.  It  is  in  the  normal  person 
that  the  withdrawal  of  even  small  quantities  of  lluid  is  apt 
to  protluce  nn])leasant  results  of  some  severity.  The  with- 
drawal of  lartje  (|uantities  of  purulent  material  is  a  sound 
physioloi;ical  and  surgical  procedure.  It  is  simply  openinj:if  an 
ali^cos.  ilrainin^-  thdrunj^hly.  luuerinm  the  pressure,  and  al- 
lowinj^  fresh  serum  containinj^  antibodies  to  pour  in  from  tiie 
blood.  It  is  obviously  not  suliicieiU  to  do  this  once,  any 
more  than  it  is  enouj:^h  to  dress  a  septic  wound  once.  The 
procedure  must  be  repeated  daily.  Even  when  serum  treat- 
ment has  been  discontinued  it  is  well  to  continue  the  spinal 
draina-^e  till  the  tluid  has  returned  to  a  fairly  normal  con- 
dition. 

After  the  administration  of  each  dose  of  serum  it  is  well 
to  rai.sc  the  foot  of  the  bed  on  blocks  so  that  the  serum  may 
the  more  readily  reach  the  brain. 

It  occasionally  happens  that  the  clinical  si^ns  point  con- 
clusively to  the  existence  of  an  obstruction  to  the  outilow 
of  the  ventricular  fluid.  In  such  cases  lumbar  puncture  and 
intra,';i)inal  administration  of  serum  are  u-^eless.  The  lateral 
ventricle  must  be  drained  and  serum  };iven  by  that  route. 
This  operation  is  not  so  diftlcnlt  as  mi.i^ht  be  imagined.  In 
the  ca.se  of  children  in  whom  the  fontanelle  is  .-till  open  the 
needle  is  introduced  at  the  lateral  angle  of  the  fontanelle.  and 
passed  (k)\\nwards  and  inwards  lor  ijj  inches.  If  the  fon- 
tanelle is  closed  a  trepine  opening  is  made  at  a  point  a  little 
behind  it  and  to  one  side  of  the  middle  line,  so  as  to  tuiss  the 
superior  longitudinal  sinus. 

The  injection  of  a  variety  of  antiseptic  substances  has  been 
tried  in  the  treatment  of  meningitis,  Ixit  none  have  given  any 
satisfaction,  rneiunococcal  and  streptococcal  cases  should  be 
treated  by  repeated  spinal  drainnge.  As  the  former  is  such 
a  fatal  illness  it  may  be  well  to  mention  a  case  reported  by 


u\ 


I'-- 


1: 


162        PHYSIOLOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

Wolff  and  Lclimann.  in  which  typical  pneumococcal  meningitis 
was  treated  by  injections  of  optochin  (ethylhydrocuprein), 
which  has  a  specilic  action  on  the  pneuniococcus.  The  drug 
was  injected  into  the  spinal  canal,  the  ventricles  and  under  the 
skin.  The  patient  made  a  good  recovery.  The  intraspinal 
(lose  was  0.03  grams. 

TUBERCULOUS  MENINGITIS 

The  treatment  of  tuberculous  meningitis  has  been  in  the  past 
one  of  nia>tcrly  inactivity.  Freciuent  lumbar  punctures  may 
relieve  the  headache,  but  fail  to  affect  the  course  of  the  disease. 
Any  new  method  is,  therefore,  worthy  of  trial.  Bacigalupo 
treated  three  cases,  in  which  tubercle  bacilli  were  present  in 
the  spinal  lluid,  l)y  intraspinal  injections  of  tul)erculin.  The 
fir-t  was  a  hopele-s  case,  for  it  was  complicated  by  general 
niiliarv  tiil)crculosis,  and  tlie  patient  could  hardly  have  been 
expected  ti)  rccn\'.r.  ( 'f  llie  dther  two  cases,  one  received  two 
and  the  otiier  three  injectinns,  and  in  the  course  of  20  days 
tbev  both  made  a  ^ood  recovery.  The  usual  dosage  of  tuber- 
culin is  employed,  depending  largely  upon  the  age  of  the 
jiatient. 

POLIOMYELITIS 

'i'lie  serum  treatment  of  i)oliomye]itis  may  be  considered 
here.  It  is  an  unfortunate  fact  that  it  has  not  so  far  been 
possible  to  produce  an  efficient  antipoli(^niyclitic  serum  from 
the  horse.  I'lcMier  found,  however,  that  the  intraspinal  in- 
jection into  an  ape  of  the  serum  of  another  ape  which  had  re- 
covered fp'in  tlie  disease  had  a  distinctly  curative  value.  He 
has  applied  the  jirinciplc  to  man,  with  encouraging  results. 
Tlie  serum  should  lie  ol>tained  if  possible  from  a  patient  who 
has  recovered  from  the  disease  within  the  last  5  years,  but  the 
amibodies  remain  in  the  blood  for  a  considerably  longer  time. 
Fnnu  ;  to  in  c.c.  shoul<l  be  injected  into  the  spinal  canal  even/ 
dav  for  S  davs.  The  scrum  should  i)e  given  if  possible  in  the 
prodromal  stage  of  the  disease. 


THERAPEUTICS 


163 


THE  INTRA-SPINAL  TREATMENT  OF  NEURO-SYPHILIS 

For  purposes  of  treatment  the  classification  of  nervous 
syphilis  into  interstitial  and  parenchymatous  is  one  of  great 
value.  The  former,  the  so-called  cerebrospinal  syphilis,  has 
always  been  recognized  as  being  amenable  to  treatment.  I-ong 
before  the  days  of  salvarsan  and  intraspinous  injections  it 
was  a  delight  to  watch  a  syphilitic  ocular  palsy  clear  up  under 
mercury  and  potassium  iodide.  The  intravenous  administra- 
tion of  salvarsan  has  rendered  the  treatment  of  this  condition 
still  more  satisfactory.  But  the  treatment  of  parenchymatous 
nervous  syphilis  —  general  paresis,  tabes  dorsalis  —  has  long 
been  the  despair  and  the  opprobrium  of  the  neurologist. 

Our  increased  knowledge  of  the  relation  of  the  neural  ele- 
ments to  the  cerebrospinal  fluid  offers  some  explanation  for 
the  inadequacy  of  treatment.  Spirocha^tcs  in  the  walls  of 
the  blood  vessels  and  in  the  meninges  can  be  readily  reached 
by  drugs  circulating  in  the  blood.  But  the  nerve  cells  are 
peculiarly  isolated  from  the  blood  stream.  They  are  bathed 
by  the  fluid  of  the  perineuronic  lymph  spaces,  which  in  its 
turn  communicates  directly  with  that  of  the  perivascular  spaces 
and  with  the  main  body  of  the  cerebrospinal  flf.Id.  The  epi- 
thelium of  the  blood  vessels  and  that  covering  the  choroid 
plexus  exerts  a  peculiar  selective  action  which  prevents  toxic 
substances  passing  out  of  the  blood  stream  and  injuring  the 
delicate  nervous  elements.  T^n fortunately  this  selective  and 
protective  mechanism  proves  the  greatest  obstacle  to  the  thera- 
peutist, for  it  frustrates  all  his  efforts  to  reach  the  nervous 
tissue  from  the  blood  stream.  .\s  a  matter  of  f.ict  even  in 
cases  of  salvarsan  poisoning  only  the  most  infinitesimal  quan- 
tities of  arsenic  have  been  found  in  the  cerebrospinal  fluid. 

In  order  to  overcome  this  difficulty  Swift  and  Ellis  devised 
the  method  which  is  known  by  their  name,  the  object  of  which 
is  to  circumvent  the  oljstacle  presented  by  the  choroid  plexus 
by  introducing  the  drug  directly  into  the  subarachnoid  space. 
It  was  considered  undesirable  to  inicct  the  dnir  in  the  pure 
form  into  the  lumbar  sac,  as  the  results  of  s(jnie  French  in- 


it-i 


^ 


■fr 


^■1 


164       nHYSIOLOOY  AND  PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

vestisators  along  tliis  line  had  not  I)cen  encouraging.  It  was 
therefore  decided  to  give  tlic  drug  intravenously,  and  after  a 
certain  interval  had  elapsed  to  withdraw  the  senim  thus  sal- 
varsanized  and  use  it  for  luniltar  injection.  The  advantage  of 
this  method  is  that  die  serum  withdrawn  contains  many  anti- 
bodies which  may  have  been  produced  liy  the  body  in  response 
to  the  action  of  tlie  salvarsan  on  the  .spirodvetes.  Its  disad- 
vantage is  that  it  is  impossible  to  be  certain  how  nnicli  salvarsan 
is  being  injected  intraspinally. 

The  details  of  the  method  are  as  follows.     The  patient  is 
given  an  intravenous  injection  of  0.5  or  0.6  gm.  of  salvarsan, 
or  a  corresponding  (luantity  of  neosalvarsan  or  diarsenol.     In 
an  hour's  time  6  oz.  of  blood  are  withdrawn.     Swift  and  Ellis 
concluded  from  their  experimental  work  that  an  hour  was  the 
interval  which  provided  the  greatest  concentration  of  antibodies 
in  the  blood.     The  blood  is  allowed  to  stand  ovemight  and 
clot.     The  serum  is  separated  and  centrifuged  thoroughly  until 
it  is  absolutely  clear  from  red  corpuscles.     This  is  of  great 
inii)ortancc,   as   the  i)resciu-e   of  ha'inoglobin   in   the   injeited 
serum  may  produce  a  violent  reaction.     The  scrum  is  care- 
fully pipetted  off,  placed  in  a  water  bath  at  -,(>'"  C.  for  half  an 
hour,  and  is  then  ready  for  injection.     Swift  and  Ellis  recom- 
mend that  it  should  be  diluted  with  twice  the  quantity  of  saline 
solution,  but  I  have  not  found  this  of  any  advantage.     They 
diluted  10  c.c.  of  serum  with  _'()  c.c.  of  normal  saline,  but  JO  c.c. 
of  pure  serum  may  be  used  without  producing  an  undue  re- 
action.    Should  the  patient  be  specially  sensitive  to  the  action 
of  the  drug,   15  c.c.  of  serum  may  be  diluted  with  15  c.c.  of 
saline.     Lumbar  puncture  is  now  performed,  and  a  quantity 
of  tluid  larger  than  the  amount  of  serum  to  be  injected  is 
drawn  off.     The  serum  is  warmed  to  body  temperature,  and 
allowed  to  run  into  the  subarachnoid  space  by  gravity  exactly 
as   in   the  administration   of   antimeningitic   serum.     During 
the  operation  the  p.'tient  should  be  in  the  recumbent  posture, 
and  when  it  is  over  the  foot  of  the  bed  should  be  raised  on 
blocks  sn  as  to  encourage  the  flow  of  serum. 

The  obvious  objection  to  the  Swift-Ellis  method  is  that  an 


THERAPEUTICS 


165 


unknown  amount  of  arsenic  is  being  injected  into  the  spinal 
canal.  This  objection,  however,  is  probalily  more  apparent 
than  real,  for  the  results  suggest  that  very  much  the  same 
quantity  of  the  drug  is  used  each  time.  A  more  serious  ob- 
jection is  that  the  patient  cannot  have  an  intraspinal  dose  unless 
he  first  receives  an  intravenous  injection.  In  cases  where  in- 
tensive treatment  is  being  used  it  may  be  possible  to  give  in- 
jections at  more  frc(iuent  intervals  by  the  intraspinal  than  by 
the  intravenous  route. 

Omlvie  accordintrlv  introduced  a  modification  of  the  treat- 
ment,  bv  which  the  salvarsan  is  added  to  the  serum  outside 
instead  of  inside  the  body.      lUood  is  withdrawn  from  a  vein 
as  before  and  the  serum  separated.     To   10  c.c.  of  serum  is 
added  from  0.25  mg.  to  0.5  mg.  of  salvarsan.  which  has  l^een 
dissolved  in  a  small  (|uantity  of  distilled  water  and  neutralized. 
The  serum  is  inactivated  for  half  an  hour  at  56"  C.  and  is  ad- 
ministered in  the  usual  way.     Salvarsan  should  also  be  given 
intravenously  every  ten  days  or  two  weeks.     From  the  point 
of  view  of  convenience  in  private  work  when  there  are  only 
one  or  two  cases  to  treat  the  Swift-Ellis  method  is  the  most 
satisfactory.     Tn  a  hospital   clinic,  however,  in  which  there 
mav  be  a  dozen  or  more  cases  the  Ogilvic  method  is  very 
convenient,   for  the  salvarsanized  serum  can  be  made  up  in 
bulk  and  given  rapidly.     .\s  regards  results  statistics  up  to 
the  present   do   not   show   any   striking  differences.     Byrnes 
of  the  Johns  Hopkins  Tlospital  has  introduced  still  another 
method,   in   wliich   be  substitutes  mercury   for  salvarsan.     It 
has  the  great  advantage  of  cheapness.     When  an  inorganic 
salt  of  mcrcurv  comes  in  contact  with  allnmien,  an  albuminate 
of  m.ercurv  is  formed.     This  albuminate  is  insoluble  in  small 
(|uantities  of  serum,  l)Ut  solultic  in  excess.     It  was  found  that 
6  c.c.   of  scrum   would  hold  0.02   gni.   in   solution.     .\   safe 
dose   for  intra-pinous  injection  is  n.0013  grm.   which  is  dis- 
solved in  the  patient's  own   scrum.     Enougli  blood   is  with- 
drawn to  vield   15  c.c.  of  serum,  and  the  scrum  removed  by 
ccntrifuging  in  the  usual  way.     In   i   c.c.  of  distilled  w.ntcr 
is  dissolved  0.00T3   grm.   mercuric  chloride,  and  the   whole 


l66        PHYSIOLOGY   AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 


■  1 


ailded  to  i  J  c.c.  of  scrum,  whicli  is  heated  at  56  C.  for  half 
an  liour.  The  mercurialized  scrum  is  injected  into  the  spinal 
canal  just  as  before. 

All  of  the  alxn'c  are  intraspinal  methods.  It  has  already 
Ix^en  pointed  out,  however,  that  although  the  flow  of  fluid  is 
from  the  spinal  canal  to  the  base  of  the  brain  it  is  also  from 
the  cortex  to  the  base.  Little  flow  apparently  takes  place 
from  below  to  above  the  tentorium.  .\s  the  chief  seat  of  the 
disease  in  paresis  is  the  cerebral  cortex  various  methods  have 
been  devised  for  l)rin<:jinij;  the  drug  into  more  direct  relation 
with  the  cortex.  Hallancc,  after  making  a  trc])liinc  opening, 
has  punctured  the  corpus  callosum  and  injected  the  salvar- 
sani/ed  scrum  directly  into  the  bitcral  ventricle.  Wardncr. 
on  the  Other  hand,  makes  a  small  opening  into  the  cerebral 
subarailinoid  space,  withdraws  30  c.c.  of  cerebrospinal  fluid, 
and  then  injects  the  salvarsanized  serum.  On  theoretical 
groimds  tliis  would  seem  to  I)e  the  most  promising  method. 
As  for  results,  time  must  be  allowed  to  tell  its  tale. 

If  the  intraventricular  method  should  come  into  vogue  it 
will  afford  an  excellent  opportunity  for  comparing  the  com- 
position of  the  ventricular  and  the  spinal  fluids.  A  few  ob- 
servations have  already  been  made  along  this  line,  and  it  has 
been  found  that  the  spinal  fluid  contains  more  cells  and  globulin 
than  the  ventricular.  Indeed  these  tests  may  be  positive  in 
the  former  iiut  ncgntive  in  the  latter.  The  Wasscrmann  and 
colloidal  gold  reactions  may  be  very  weak  in  the  ventricular 
but  (|uite  intense  in  the  spinal  fluids.  Further  observations 
on  differences  in  the  two  fluids  occurring  in  various  forms 
Oi"  disease  are  greatly  to  be  desired. 

In  judging  the  effects  of  treatment  upon  a  case  of  neuro- 
sv]ihilis  attention  must  be  paid  f  i )  to  tlie  clinical  condition 
of  the  patient  and  (2)  to  the  pathological  changes  in  the  spinal 
fluid.  It  is  important  tn  bear  in  mind,  however,  that  spontane- 
ous rcnii^^^iou-^  mav  ocrtir  in  the  clinical  course  both  of  tabes 
and  paresis.  It  is  well  known  that  a  case  of  paresis  may 
occasionaliv  show  an  extraordinary  temporary  improvement 


THERAPEUTICS 


167 


in  his  mental  and  physical  condition.  Such  remissions  may 
last  from  several  months  to  a  year.  Similar  inexplicable 
periods  of  improvement  may  also  occur  in  tahes.  1  f  the  spinal 
fluid  be  examined  during  these  intervals  it  will  never  be  found 
to  have  returned  to  normal.  Mitchell.  Darling,  and  Xew- 
comb,  however,  found  from  repeated  observations  on  selected 
cases  that  the  cell  count  may  lluctuate  to  a  remarkal)le  degree. 
In  several  of  their  untreated  cases  of  paresis  the  cell  count 
varied  on  different  occasions  from  i  to  over  100.  These 
various  facts  must  ])e  borne  in  mind  in  forming  a  critical 
judgment  of  the  effects  of  treatment  in  neuro-syphilis,  for 
sometimes  the  spontaneous  improvement  both  clinical  and 
cytological  would  deceive  the  very  elect. 

Even  when  the  subject  is  approached  in  this  critical  mood, 
however,  the  results  of  the  new  methods  of  treatment  are  in 
many  cases  calculated  to  make  the  most  skeptical  enthusiastic. 
The  results  in  cerebrospinal  or  interstitial  syphilis  are  brilliant, 
as  was  to  be  expected.  Walker  records  a  case  of  syphilitic 
meningitis  in  which  the  cell  count  dropped  from  9,^00  to  1 26 
after  three  intraspinal  injections.  In  the  early  stages  of  cere- 
brospinal syphilis  it  may  appear  hardly  necessary  to  resort  to 
intraspinal  medication,  for  by  intravenous  treatment  alone  the 
symptoms  may  be  completely  relieved,  the  cell  count  return  to 
normal,  and  the  Wassermann  reaction  no  longer  be  obtained 
even  with  i  c.c.  of  fluid.  It  is  always  wise,  however,  to  give 
a  few  intraspinal  injections.  Chronic  and  long  standing  cases 
mav  show  some  symptomatic  improvement  with  intravenous 
treatment,  but  the  spinal  fluid  is  not  affected  until  the  in- 
travenous are  combined  with  intraspinal  injections.  The  cell 
count  is  the  first  of  the  pathological  conditions  to  be  affected, 
and  it  can  be  watched  dropping  week  by  week  until  it  reaches 
normal.  .\s  Walker  has  pointed  out,  it  is  the  endothelial  cells 
which  arc  the  first  to  go,  followed,  at  a  short  interval,  by 
the  small  lymphocytes.  The  globulin  is  more  difficult  to  in- 
fluence. .After  repeated  injections,  however,  it  also  can  usually 
l)c  reduced  to  norm.il.     The  W^1ssc!•mann  is  the  most  obsti- 


i()8     riivsioi.or.v  and  i'atiioi.cx'.v  or  Tiir  cirimirosimn  \i.  fluid 


;;  *. 


natc  (if  tlu'  cli;ini;o>.  In  xniio  oa-cs  it  will  he  fdiuid  iiiipossililc 
ti)  ali(ili>li  it.  .\>  a  nik',  Imwivcr,  tnainuut  will  rcMilt  in  a 
lliiid  wliiili  will  i;i\L'  a  iii'i^ativi'  ri.uiinn  with   i  ca". 

Hut  it  is  with  regard  to  it>  sua-<.'>s  in  the  iian.Micli>niatcms 
t'ornis  (if  ncnni---\i)hilis  that  any  new  treatment  must  stand 
or  fall.  What  impe  has  the  new  therapy  tn  offer  to  the  vic- 
tiin>  of  paresis  and  talies?  Not  a  certainly  of  cure.  'I'liat 
was  hardly  to  be  hoped  I'or,  and  certainly  never  claimed.  Ihit 
at  least  the  >tronL;  pmlialiility  that  the  >yniptonis  will  Ijc  to 
some  extent  alleviated,  the  course  of  the  disease  stayed,  and 
tlie  pos^iliility  that  in  favorahle  case^  an  actual  cure  may  he 
adiieved.  .\nd  can  more  than  this  lie  done  in  ili>e,i-es  of  the 
heart,  kidney  or  paticrea-?  ( )nce  the  iiarenchymatous  tissue 
of  an  origan  has  been  replaced  by  inler>titial  tissue  no  power 
on  earth  can  make  that  ori;:an  norm;d  a,i;;ain,  If.  liowever,  ihe 
injurious  aj;ent  be  removed  or  destroyed  further  downward 
]iro,tiTess  may  be  arrested. 

Xo  one  who  has  lonked  at  the  brain  of  an  advanced  paretic 
or  at  tile  posterior  column^  of  a  tabetic  cord  will  expect  paticnt.s 
sufferin,t:j  from  these  disease-  to  be  restored  to  a  normal  condi- 
tion. I'lvervthiui;  (kMiends  on  the  >taiie  of  the  disease  at  which 
treatment  is  commenced.  .\s  (.'otton  rem.arks.  the  varyins^ 
results  obtained  by  those  practicing  the  treatment  depend 
rather  on  the  statue  of  the  disease  than  on  the  modification 
of  treatment  used.  Cases  seen  in  private  or  in  a  neurological 
clinic  w  ill  naturally  i,nve  very  different  results  from  inmates  of 
asvlums  who  are  passing:;  into  a  state  of  dementia. 

The  (|uestion  of  tlie  very  earliest  diat^nosis  of  paresis  and 
talies  is  therefore  of  incalculalile  importance,  for  it  is  in  the 
verv  earlv  stajje  that  there  is  a  chance  of  com])Ictely  arresting 
the  course  of  the  disease  and  rcstorin.u;-  the  p.atient  to  health. 
The  results  have  been  most  satisfactory  in  tabes,  considerably 
les.s  so  in  paresis.  V.wn  in  the  latter,  however,  astonishing 
im|)rovement  sometimes  results.  Thus  Cotton  records  the  case 
of  a  German  woman  sutterint;-  from  paresis  who  was  admitted 
to  the  asvlum  in  a  state  of  acute  excitement.  The  four  re- 
actions of  Nonne  were  positive.     On  admissiim  .she  was  un- 


TlliRAI'tUTICS 


169 


able  to  s])cak  a  word  of  I'?n},'lish.  After  a  course  of  intra- 
spinal treatment  she  made  a  good  recovery,  learned  I'".nj,disli, 
and  when  she  was  dischar^'ed  she  was  able  to  converse  lluently 
in  that  lanj,niaf,'e. 

Tabetics  may  coiitideiitially  expect  to  receive  very  preat 
svmptoniatic  relief.  The  severe  pains  which  arc  so  distress- 
in}";  a  feature  of  the  disease  are  usually  relieved  in  a  remark- 
able detjree  and  often  completely  abolished.  The  };;astric 
crises,  attacks  tif  giddiness,  headaches,  bladder  disorders  and 
other  troubles  are  often  ijrcatly  improved.  I'.ven  the  ataxia 
may  become  considerably  less. 

The  spinal  lluid  is  more  resi>teiit  to  treatment  than  in  the 
case  of  cerebrospinal  syphilis,  but  if  the  treatment  be  ])er- 
sisted  in  it  will  ultimately  res])on(l.  In  early  cases  the  cell 
count  and  globulin  can  be  reduced  to  normal,  and  in  some  in- 
stances the  \\  as>ermann  reaction  may  become  net^ative  with 
I  c.c.  C"ase>  of  Ioniser  standin.sj;  will  cause  mor-  trouble,  and 
it  mav  be  impossible  to  abolish  the  positive  Wassemiann. 
I'suallv.  however,  it  can  be  j^reatly  diminished  in  intensity. 
The  ca-es  which  respond  best  to  treatment  are  those  in  which 
the  cell  coinit  is  hii^hest.  indicatini;  probably  that  a  marked 
menini^'eal  element  is  present.  In  such  ca.ses  the  rapid  fall  in 
the  number  of  cells  is  t^encrally  accompanied  by  a  correspond- 
in}::  imjji'ivement  in  the  clinical  condition. 

It  is  in  ])aresis,  as  was  to  l)e  expected,  that  the  greatest 
dift'culties  are  ex|)erienced.  Xothing  can  be  hoped  for  in 
advanced  cases.  It  is  to  the  early  cases  —  indeed  the  very 
earliest  possible  cases  —  that  we  nuist  look  if  we  wish  to  .stay 
the  course  of  the  disease.  In  these  cases  results  have  already 
been  obtain  which  indicate  that  the  future  of  the  paretic  is 
not  now  as  hopeless  as  it  has  been  in  the  past.  And  even  in 
cases  which  have  passed  this  earliest  stage  a  long  series  of 
injections  should  certainly  be  tried,  for  both  the  mental  and 
phvsical  condition  mav  occasionally  show  astonishing  improve- 
ment. The  tremors  may  disappear,  the  handwriting  may 
change  from  an  illegible  scrawl  to  an  example  of  good  pen- 
manship, and  the  mental  improvement  may  be  so  great  that 


i7»)     nnsioi.oiiv  anij  patiioiocv  ok  tiii;  ckribrosimnai,  fix'id 


1i. 


!: 


tlic  patient  is  alilc  to  return  to  liis  Ikiiuc  life,  ami  perhaps  even 
resume  hi-,  civil  (iccupatiiii.  In  >h(irt,  the  CDnihined  intra- 
>]iinal  and  intravenous  salvarsan  treatment  has  acconiplisiied 
for  ^aiKial  paresis  uliat  no  otiier  form  of  treatment  has  ever 
done  hefore.  it  is,  however,  very  necessary  still  to  preserve 
a  critical  attitmle  to\vard>  the  whole  matter,  for  the  introduc- 
tion (if  any  new  therapeutic  measure  has  always  been  followed 
by  reports  of  many  successful  cases,  it  is  only  later  that 
we  hear  of  the  failures. 

it  is  difficult  to  say  how  lonj;  the  treatment  .sliould  !)C  con- 
tinued. I'Aerythinjj  depends  on  the  individual  case,  the  im- 
provement in  the  clinical  condition,  and  the  response  of  the 
s])inal  lluid.  Just  as  a  ])hy>ician  nowadays  should  not  feel 
satisfied  with  his  treatment  of  a  case  of  diabetes  until  he  gets 
the  urine  completely  suf^ar  free,  so  in  the  treatment  of  neuro- 
sxphilis  it  should  lie  the  ambition  of  the  doctor  to  get  the 
cercbros])inal  lluid  cell  free,  globulin  free,  and  if  possible  with 
a  negative  \\  assermann. 

Occasionally  it  may  h;i])])en  that  treatment  is  too  energetic 
and  intense,  with  the  result  that  a  meningeal  reaction  is  pro- 
duced. The  patient  (levelo])s  severe  headache  and  other  signs 
of  meningitis,  and  the  ,s])inal  lluid  shows  a  very  marked  pleo- 
cvtosis,  most  of  the  cells  being  polymorphs.  These  changes, 
however,  arc  only  transient  and  are  merely  an  indication  that 
the  treatment  must  be  pursued  with  less  energy. 


fir 


TETANUS 

There  is  .-till  no  specific  curative  treatment  for  tetanus. 
.\II  that  we  can  do  is  to  try  to  control  tlie  convulsions,  and 
tide  the  patient  over  the  immediate  danger  of  respiratory 
])aralvsis.  I"or  this  ])urpose  our  most  efficient  remedy  is  the 
intraspinal  injection  of  magnesium  suli)hate.  .\  25  per  cent. 
solution  of  magtie-ium  sulphate  is  ])reparcd  and  warmed  to 
bndv  tem])eraturc.  Of  this  solution  1  c.c.  is  used  for  every 
jin  lbs.  of  bodv  weight.  The  patient  is  put  under  a  general 
ana'sthelic  and  a  quantity  of  corcbro-pinal  lluid  withdrawn 
ecpial  in  bulk  to  the  amount  of  solution  which  it  is  intended 


THERAI'EfTICS 


I7« 


ti»  inject.  Relief,  evidenced  l)y  complete  relaxation  which 
tnay  last  for  24  hours,  is  often  obtained  at  once,  owing  to  the 
depressant  action  of  the  magnesium  sulphate  on  the  lower 
motor  centers  in  the  cord.  If  the  symptoms  recur  a  second 
but  smaller  dose  should  be  piveii,  0.8  c.c.  for  every  -'o  lbs. 
The  chief  danger  is  respiratory  paralysis.  If  this  occurs  a 
large  ([uantity  of  cerebrospinal  fluid  should  at  once  lie  with- 
drawn, and  the  subarachnoid  sac  washed  out  with  normal 
saline,  the  head  being  kept  well  elevated. 

It  will  be  seen  that  at  present  the  therapeutics  of  the  cerebro- 
spinal lluid  fall  under  two  headings:  (  i)  drainage  of  the  fluid 
and  (2)  injection  of  certain  sera  and  drugs.  Excellent  re- 
sults have  Ijeen  obtained  in  certain  conditions  and  the  outlook 
is  very  bright.  The  method  of  intraspinal  injection  in  par- 
ticular is  capable  of  great  expansion,  and  the  therapeutic  pos- 
sibilities are  extremely  encouraging.  Before  the  full  l)enefits 
of  this  measure  can  be  reaped,  however,  it  is  necessary  that 
our  knowledge  of  the  origin  and  destination,  the  ebb  and  flow, 
the  streams  and  channels,  and  the  c  •  •  of  circulation  of  the 
fluid  should  be  still  more  extended  a:      systematized. 


REFERENCES 

Rabinski,  J.:  Sur  le  traitcment  dcs  affections  de  I'orei'lc  et  en 
particulaire  du  vertige  atiriculaire  par  la  rachicentese.  .Ann.  des 
Mai.  dfc  roreille.,  1904,  XXX.  p.  loi. 

Racigalupo,  J. :  Eine  neue  Behandlungsmethode  der  Tubcrkulosen 
Meninfjitis.     Miinch.  med.  Wclinsclir.,  1915,  LXIT,  p.  222. 

Hallancc,  C.  A. :  A  method  by  means  of  wliich  remedial  agents 
may  be  mingled  with  'he  cerebrospinal  fluid.     Lancet,  1914.  I.  P-  ^5-5- 

Ryrnes,  C.  M. :  The  intra-dural  administration  of  mercurialized 
serum  in  the  treatment  of  cerebrospinal  syphilis.  Jour.  Am.  Med. 
Assoc,  1914.  LXVII,  p.  2182. 

Costa,  R.:  Punctura  Lombare  nel  feto  duranto  I'estrazione 
podalica  nell'  interesse  della  vita  del  feto  stesso.  Gazette  degli. 
Ospedali  a  delle  Clinicke.  Milan.  Sept.  3,  1916,  XXXVII. 

Cotton.  The  treatment  of  paresis  and  tabes  dorsalis  by  salvar- 
sanizcd  scrum.  Amer.  Jour.  Insanity,  1915,  LXXII.  pp.  125,  355, 
and  485. 


172        I'MVSIOLOCY  AM)   I'ATIIOLOGY  OF  TIIK  LhRKBROSI'l VAI.   KI.UID 

FiscliiT,  I.,;  C'utivulsions  iliirinj;  |icrtiis>is.  New  ^'<lrk  Med. 
Jour..  1014,  ('.  p.  1054. 

Mitchi'll,  II.  W..  Darlinj,',  A.,  and  Xeucoinli,  I'.  !!.:  ( )liscrv,itinii 
iipcjti  spinal  rtniil  ci'U  cniiuts  in  mitrcattil  ca>>CN  of  ecnlifospiiial 
syphilis.     Jour.   N'crv.  and   Mental   Dis..    1014,   XI, I.  |).  (>H(t. 

ORilvie,  II.  \'. :  The  intra<i>inal  treatment  of  syphilis  of  tjie  con- 
tra! nervous  system  with  salvarsanized  sirum  of  standard  stren^lh. 
Jour.  .\m.  Med.  .Assoc.,  1914.  I. XIII,  p.  22. 

0>;ilvie,  II.  S. :  The  treatmi'iu  of  ^;encr.al  (larcsis.  ,\m.  Jour. 
Syphilis,   1917.     I.  p.  509. 

Swift.  II.  F.  and  Fllis.  .\.  \V.  M.:  The  dinct  treatment  of 
syphilitic  diseases  of  the  central  nervous  system.  .New  ^'ork  Med. 
Jour.,   i()ij,   X(\I,  p.  5,^. 

I^wift,  11.  F. :  Observations  on  types  of  response  in  treatnicnt  of 
syphilis  of  the  central  nervous  system.  .\mer.  Jour.  Syjiliilis,  1917, 
I    p.   5J4. 

Walker.  I.  C.  and  Haller,  D.  .\  :  The  tre.itniont  of  syphilis  of 
the  centra'  nervous  system  »vitli  intravenous  salvarsan  alone,  with 
intravenous  salvarsan  and  intraspinal  salvarsanized  serum  together, 
and  with  intraspinal  salvarsanized  serum  alone.  Arch.  Int.  Med., 
1016.  XVIII,  p,  376 

Wardncr,  I).  M. :  A  report  of  5  cases  of  the  intracranial  iniec- 
tion  of  autosero  salvarsan.     .\in.  Jour.  Insanity.  H)i.^.  I.XNI.  p.  .j;!). 

Wilson,  W.  T. :  l.nmhar  piuicturc  for  the  relief  of  convnlsiims  in 
puerperal  eclampsia.     Jour.  .Am.  Med.  .Assoc,   1016,  I.XX'II.  p.  742. 

Wolfif,  S.  and  I.chmann,  W.:  I'ber  eincn  durch  intralumliale  und 
intravcntriculare  .Acthylhydrf)cuprein  Iiijektioncn  jreheiltcn  Fall  von 
Pncumokokkenmeninpitis  Dcut.  mcd.  Wchnschr..  Tf)i,v  XXXIX,  p, 
2509. 


! 


ADDITK  i.\.\L  KF.FF.RKN'CES 


Ayer,  J.  H. ;  Luinhar  puncture  and  examination  of  the  spinal 
fluid  ill  alTcctions  of  the  eye.  Arch,  of  Ophthalmology,  1916,  XLV, 
Xo.  I. 

AyiT,  I.  M.  and  Victs,  II.  R.:  Spinal  fluid  findings  characteristic 
of  cord  coini)rcsNion.     Jour.  .Vm.  Med.  .Assoc.  1916,  LXVII,  p.  1707. 

itarbet,  I".  H.:  l-inding  of  arsenic  in  the  cerebrospinal  fluid  fol- 
lowinj;  intravenous  administration  of  neosalvarsan.  Calif.  State 
Jour,  of  Medicine.   iqi6,  XIV,  No.  it. 

liaumel.  J.;  La  ponction  lonibairc  dans  les  commotions  nerveuses 
et  Us  tra.iinatisnies  due  crane  par  projectile.s  de  guerre.  Lyon, 
cliir.    1015,   XII,  p.  271. 

Mioch,  L. :  The  value  of  spinal  puncture  in  the  etiologic  diagnosis 
01  cardiovascular  diseases.  Jour.  .Am.  Med.  Assoc.  1917,  LXVIII, 
p.  691. 

Fironstein,  Boris:  Acute  syphilitic  meningitis.  International 
rii-'ics.    Kjifi,  Vol.  IV,  p.  23. 

'.ch.  .A. :     Some  modern  views  of  syphilis  of  the  nervous  system. 
Jon      Am.  Med.  .Assoc,  1916,  LXVI.  p.  1596. 

Collins,  J. :  Tathognomonic  alterations  of  the  cerebrospinal  fluid 
in  syphilis  of  the  nervous  system.  An.  Jour.  Med.  Sc,  1916,  CLI, 
p.  222. 

Dana,  C.  L. :  Puncture  headache.  Jour.  .Am.  Med.  Assoc,  1917, 
LXVIII,  p.   1017. 

Dcmole,  v.:  Coagulation  and  xanthochromia  in  compression  of 
the  .spine  by  a  tumor.     Rev.  ncurol.,  1915,  XXII,  p.  649. 

Dercum,  F.  X.:  Metabolism  in  insanity.  Jour.  Am.  Med.  Assoc., 
1916,  I.XVI,  p.   n86. 

Dinar,  J.:  Observations  on  the  cerebrospinal  fluid  in  poliomyelitis. 
Med.  Times,  1916,  XLIV,  p.  287. 

Donaldson,  R. ;  An  improved  type  of  needle  for  lumbar  puncture. 
Lancet,  19 16,  CXCI,  p.  982. 

Elser,  W.  J.  and  Iluntoon,  F.  M. :  Studies  on  meningitis.  Jour. 
Med.  Research,  1909,  XX,  p.  371. 

Ciilpin,  S.  F.  and  Farley,  T.  B.:  Drainage  of  cerebrospinal  fluid 
as  a  factor  in  the  treatment  of  nervous  syphilis.  Jour.  Am.  Med. 
Assoc,  1916,  LXVI,  p.  260. 

Ciolla,  F.  L.  and  Symes,  W.  L. :  Simultaneous  records  of  cerebro- 
spinal pressure  and  of  respiratory  movements.  Jour.  Phys.,  1916, 
L,  No.  5. 

Halverson,  J.  O.  and  Bergeim,  O. :    The  calcium  content  of  the 

173 


I  .; 


I: 


174       PHYSIOLOGY  AND   PATHOLOGY  OF  THE  CEREBROSPINAL  FLUID 

cerebrosi)iiial  fluid  particularly  in  tabes  dorsalis.  Jour.  Biol.  Chem., 
19 1 6,  XX I. \,  p.  337. 

Ilort,  E.  C. :  The  meningococcus  of  W'eichsclbaum.  Hrit.  Med. 
Jour..  1017,  II.  p.  7,yy. 

Kafka,  v.:  UcIkt  tlen  licutiRcn  stand  der  Licpiordiagnostik. 
Miinch.  mod.    Wocli.    ii>i5.   LXII,   p.    105. 

Kalin,  R.  L. :  Folin  and  Denis'  method  of  nitrogen  determinations 
by  direct  Xesslerization  and  its  application  to  si)inal  fluids.  Jour. 
Biol.  rhem..    i<)i6,  XXVIII.  p.  203. 

I. abbe,  Zisliii.  and  Cavaillon :  I.es  nieningites  cerebrospinales  et 
lenr  traitcment  par  la  trepanation  et  I'injection  de  scrum  intraventri- 
culairc.     Bull,  de  I'.Xcad.  de  Med..  1916,  LXXV,  Xo.   u. 

Leopold,  J.  .^.  and  Heriiliard,  A.:  Chemistry  of  s])inal  fluid  in 
children.     Am.  joiir.   I)is.  Child.,   1917,  XIII,  p.  34. 

Levinson.  .\. :  .\  uniform  method  for  collection  of  spinal  fluid 
into  test  tubes.     Med.  Record,  1916,  I, XXXIX,  \o.   17. 

Meltzer.  .^.  J. :  Inhibitory  properties  of  magnesium  sulphate  and 
their   therapeutic   application    in    tetanus.    Jour.    .Xm.    Med.    .\ssoc., 

1916,  I, XVI,  p.  933. 

-Xobel,  K. :  L'ntersuchung  tiiberkul<">s  mcningitischer.  Punktions- 
fliissigkeiten  mit  llilic  der  .Xinhydrinreaktion.  Miinch.  med.  W'och., 
1915,  Xo.  52. 

Reece.   R.    J. :     .Anthrax   simulating  cerebrospinal    fever.     T.ancet, 

1917.  CXCII.  p.  406. 

Schlos.s,  O.  M.  and  .'^chroeder,  L.  C. :  Xatnre  and  quantitative  de- 
termination of  the  reducing  substance  in  normal  and  pathologic 
cerel)rosi)inal  fluid.     .\m.  Jour.  Dis.  Giild..   1916.  XI,  p.   I. 

Simon,  G. :  Zur  Untersuchung  der  I-iquor  cerebrospinalis  nach 
Mayerlioftr.     Wein.   klin.    Woch.    191 1.   XXI\',   p.   94. 

.Stern,  C. :  \'crleichcnde  I'ntersnchungen  iiher  die  Thoma- 
Zeiss'sche  und  Fuchs-Rosenthal'schc  Zidilkammer  bei  Liquorunter- 
suchungen.     Miinch.  med.  W'och..   1916,  LXIII,  Xo.  3. 

Stevens  II.  C. :  The  spinal  fluid  in  Mongolian  idiocy.  Jour. 
;\m.   Med.  Assoc.   1916.  LXVI,  p.   1373. 

Stoddard  and  Cutler:  Torula  infection  in  man.  Monographs  of 
the  Rockefeller  Institute.     \o.  6,  1916. 

Taylor,  F.  E.:  The  nntiliody  content  in  meningeal  infections. 
Lancet.   1917,  CXCII,  p.  418. 

Torrey,  R.  C. :  Influenzal  meningitis.  .*\m.  Jour.  Med.  Sc,  1916, 
CI. 1 1,  p.  403. 

Weston,  r'.iul  C,. :  Reaction  of  the  cerebrospinal  fluid  in  the 
psychoses.     Jdur.  Med.   Research,   1917.  XXXV,  p.  367. 


INDEX 


Absorption  of  cerebrospinal  fluid, 
i8 

Acetone  in  cerebrospinal  fluid,  146 

Alcoholism,  145 

Ammonium  sulphate  test  for  globu- 
lin, 51 

Arachnoid  villi,  9,  20 

Racteriology  of  cerebrospinal  fluid, 

86 
niood  in  cerebrospinal  fluid,  41 

Carbon  dioxide  as  stimulant  to  flow 

of  cerebrospinal  fluid,  25 
Cerebral  abscess,  124 
Cerebral  b.Tmorrhapc,  126 
Cerebral  thrombosis,  127 
Cerebral  tumor,  123 
Cerebrospinal  rhinorrhcea,  18 
Cells,  differentiation  of,  by  Alzheim- 
er's method,  65 

methods  of  counting,  60 

origin  of,  70 

varieties  of,  67 
Chorea,  148 
Choroid  plexus,  12 
Circulation   of   cerebrospinal    fluid, 

23 
Colloidal  gold  reaction,  79 

in  cerebrospinal  syphilis,  114 

in  general  paresis,  119 

in  acute  poliomyelitis,  137 
Composition  of  cerebrospinal  fluid, 

49 
Concussion,   131 
Counting    chamber,     Fuchs-Roscn- 

thal,  62 
Cytology  of  cerebrospinal  fluid,  fio 


Dementia  praecox,   144 
Diabetes  mellitus,  146 


Echinococctis  cyst  of  brain,  123 
Electrical   conductivity,  46 
Encephalitis  lethargica,  127 
Epilepsy,  144 
Erythrochromia,  43 

Freezing  point.  45 

Function  of  cerebrospinal  fluid,  29 

General  paresis,  117 

juvenile   form,    120 
Globulin,  50 

in  acute  poliomyelitis,  136 

in  general  paresis,  118 

in  meningococcal  meningitis,  95 

in  tabes  dorsalis,  116 

in  tuberculous  meningitis,  107 

tests  for,  51 
Gold  reaction  of  Lange,  70 

Herpes  zoster,  141 
Hydrocephalus,  treatment  o*    130 

varieties  of,  129 
Ilydrogen-ion  concentration,  46 

Idiocy.  145 
Insanity,  143 

Jaundice,  45 

Langc's  colloidal  gold  reaction,  79 
Lumbar     puncture    as     therapeutic 
measure,  155 
after  effects,  38 
Lymphocytosis  in  acute  poliomyeli- 
tis, 136 

in  general  paresis,  117 
in  mumps.  140 
in  tabes  dorsalis,  IT5 
in  turberculous  meningitis,  102 


I7S 


176 


INDEX 


VJ 


s 


if* 


;• 


hk 


Manic-depressive  insanity.  143 

Mastic  test,  84 

Meningitis,  meningococcal,  92 

pneumococcal,  97 

serous,   105 

scrum  treatment  of,   158 

staphylococcal,  104 

streptococcal.  99 

typhoid,  104 

tuherculnns,  100 
Meningococci,   methods  of  culture, 

04 
Multiple  sclerosis,  141 
Mumps,  149 
Myelitis,  acute,  135 

Nature  of  cerebrospinal  fluid,  31 
Noguchi  test  for  globulin,  52 
Xonne-Froii    ^yndrnme,  133 
Xonnc  test  for  globulin,  51 

(Edema  of  brain,  131 

Origin  of  cerebrospinal  fluid,  14 

Pacchionian  bodies.  7 
Pnndy  test  for  globulin,  5:: 
Permeability  of  meninges.  26 
Physical  properties  of  cerebrospinal 

fluid.  41 
Pituitary   gland,    secretion    of    pos- 
terior lobe,  18 
Pneumonia,   cerebrospinal   fluid   in, 

151 
Poliomyelitis,  acute  anterior,  131 
Potassium  permangan.Tte  index,  53 
Pressure,  methods  of  determining, 

34 
Protein  content,  50 

Reaction,  46 


Spinal  cord  tumor,  133 

Subacute     combined     degeneration 
140 

Subarachnoid  space,  anatomy  of,  6 

Sugar,  55 
in  acute  poliomyelitis,  137 
in  diabetes  mellitus,    146 
in  general  paresis,   1 17 
in  meningococcal  meningitis,  95 
in  tuberculous  meningitis,   lOl 

Swift-Ellis    method    of    treatment, 

1^-3 
Syphilis,  cerebrospinal,   1 13 

early  ui 
Syphilis    of    the    nervous    system, 

treatment  of,   1O3 
Syringomyelia,   135 

Tabes  dorsalis,  T14 
Tetanus,  treatment  of,  170 
Trichiniasis,   152 
Tuberculous  meningitis,   too 

treatment  of,   162 
Tubercle  bacilli,  demonstration   of, 

102 
Turbidity,  43 

Urea,  58 

estimation  of,  148 
Uremia.  146 

I'rotropin,    excretion    of,    in    cere- 
brospinal  fluid,  26 

Ventricles,  anatomy  of,  12 

Wasserniann  reaction.  73 
in  cerebrospinal  syphilis,  113 
in  early  syphilis,  112 
in  general  paresis,  119 
in  tabes  dorsalis,   116 


Sleeping  sickness,  151 
Specific  gravity,  46 


Xanthochromia,  43 

in   turrvor  of  spinal  cord,   133 


rKISTED    IS    THE    VNITED    6TATES    OF    AMERICA 


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